Pharmacology of human ASIC1a channels on Nanion’s SyncroPatch 384i - Application Note

200928 blog image ASIC1a app note

Summary

Acid-sensing ion channels (ASICs) are protongated Acid-sensing ion channels (ASICs) are protongatedion channels which are highly sensitive toextracellular acidosis and are permeable tocations, predominantly Na+. They are members of thes odium-selective cation channels belonging to the epithelial sodium channel/degenerin (ENaC/DEG) family.

Data and Applications

KCa1.1 (BK) - High throughput study

KCa1 1 SampleTracesicon sp96   SyncroPatch 384i data and applications:
Data kindly provided by Sharan R. Srinivasan1 and Vikram G. Shakkottai1,2
1Department of Neurology, University of Michigan, Ann Arbor, MI 48109;
2Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.

HEK293 cells stably transfected with BK channels were used to screen over 50,000 compounds, and using clever buffering techniques, targeting only activators of calcium sensitivity for BK channel augmentation. 

Read more

 

P2X2/ P2X3 - Block by suramin on the SyncroPatch 384PE

P2X23 CHO Cells suramin SP384icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) data and applications: 
Cells were engineered and kindly supplied by Axxam

P2X2/3 recorded from CHO cells on the SyncroPatch 384PE. P2X2/3 was activated by 10 µM ATP and blocked by increasing concentrations of suramin with an IC50 = 17.7 ± 0.9 µM (n = 372). Average traces and concentration response curve shown for 372 cells. Success rate was 97% for completed experiment (372 wells from a possible 384). Multi-hole (4 holes per well) chips were used.

P2X2/ P2X3 - High throughput screening on the SyncroPatch 384PE

P2X23 CHO Cells Suramin SP384 Screenshoticon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) data and applications: 
Cells were kindly supplied by Axxam

Inhibition of P2X2/3 by suramin. Suramin was pre-incubated at each concentration for 3 - 5 mins followed by co-application with 10 µM ATP. All 3 concentrations of suramin were applied to each well and a cumulative concentration response curve was constructed for n = 372 wells out of a possible 384. Success rate was 97% for completed experiments. .

P2X2/ P2X3 - Activation by ATP on the SyncroPatch 384PE

P2X23 CHOCells ATP SP384icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications: 
Cells were kindly supplied by Axxam

P2X2/3 recorded from CHO cells on the SyncroPatch 384PE. P2X2/3 was activated by increasing concentrations of ATP with an EC50 = 1.1 µM (n = 191). ATP was applied for approximately 1.5 s using the ‘Ligand Puff’ function of the SyncroPatch 384PE. Average traces and concentration response curve shown for 191 cells. Success rate was 99% for completed experiment (191 wells from a possible 192). Multi-hole (4 holes per well) chips were used.

AMPA Receptor (GluA2) - Pharmacology

icon sp96   GluR2 PE Data PharmacologySyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by SB Drug Discovery.

The AMPA receptor (GluA2) was analyzed using different positive and negative allosteric modulators (CNQX, LY404187, LY395153, CP465022, Cyclothiazide). After activating the receptor by application of Glutamate, the modulating compound plus glutamate was applied afterwards. Measured on the SyncroPatch 384PE the whole cell patch methodology and multi-hole chips were used.
The lower images on the left hand side are displaying a screenshot of a current after application of the positive modulator LY404187. The EC50 was determined as 379 nM.

AMPA Receptor (GluA2) - Activation by Glutamate

icon sp96   GluR2 PE DataSyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by SB Drug Discovery.

The AMPA receptor (GluA2) was activated using different concentrations of glutamate (1 µM - 100 µM). Measured on the SyncroPatch 384PE the whole cell patch methodology and multi-hole chips were used.
The lower two images are displaying screenshots of single cell currents after repetitive glutamate applications:
Left: The same concentration of Glutamate was applied three times.
Right: Four different Glutamate concentrations were applied in a cumulative manner.

AMPA Receptor (GluA2) - Cumulative Concentration Response

icon sp96   GluA2 GluCRC SP384PE SBSyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by SB Drug Discovery.

The AMPA receptor (GluA2)was activated by increasing concentrations of glutamate on the SyncroPatch 384PE. L-glutamate was applied for approximately 500 ms in increasing concentrations (A) and a cumulative concentration response curve for glutamate was constructed for 222 wells (C).
The online analysis values peak amplitude and area under the curve (AUC) are shown versus time in Panel B. The fast activation of GluA2 could be captured at higher concentrations (inset; 1 mM).

NaV1.8 - State Dependent Inhibition

icon sp96   PE NaV1.8 State dep InhibitionSyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

The state dependent inhibition of Tetracaine on NaV1.8 currents were investigated. Measured on the SyncroPatch 384PE the perforated cell patch methodology (Escin) and multi-hole chips were used and compared to single-whole chips. Using a state dependant pulse protocol, the IC50 value determined from the first pulse (C1) was calculated as 54.3 µM (Hill coefficient = 1.50), and from the second pulse (C2) as 1.27 µM (Hill coefficient = 0.62). 

 

NaV1.7 - Frequency Dependent Inhibition

icon sp96   PE NaV1.7 TetracaineSyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Anaxon.

The frequency dependent inhibition of Tetracaine (5 µM, 15 µM and 50 µM) on NaV1.7 currents were investigated. Measured on the SyncroPatch 384PE the whole cell patch methodology and single-hole chips were used. The IC50 value determined from the first pulse of the pulse train was calculated as 41.8 µM, from the second pulse as 9.9 µM and from the 10th pulse as 3.0 µM. 

 

NaV1.7 - Pharmacology of Lidocaine

icon sp96   PE NaV1.7 LidocaineSyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Anaxon.

The effect of different concentrations of Lidocaine on NaV1.7 currents were investigated. Measured on the SyncroPatch 384PE the whole cell patch methodology and single-hole chips were used. The success rate of > 90% for cells which had a seal resistance > 500 MΩ was determined. A value of 0.79 was calculated for the z-factor (characterization of HTS screening assay quality).

NaV1.5 - Late Current Analysis using the CiPA Protocol

CiPA PE NaV1 5 Pharmacology late currenticon sp96   SyncroPatch 384/768 PE (a predecessor model of the SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing NaV1.5 current traces in response to the CiPA voltage step protocol, measured on the SyncroPatch 384PE using whole cell patch clamp methodology and single-hole chips. The NaV1.5 late current was activated by the application of 60 nM ATX-II. The IC50 value of Ranolazine of the late Sodium current current was determined as 40.4 µM.

 

hERG - Pharmacology at Physiological Temperature using the CiPA Protocol

CiPA PE hERG Pharmacology 35DegreeCelsiumicon sp96   SyncroPatch 384/768 PE (a predecessor model of the SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol at 35 degree Celsius. Measured on the SyncroPatch 384PE using perforated patch clamp methodology (Escin) and multi-hole chips (4 holes per well). The IC50 value of Erythromycin of the peak current was determined as 60.5 µM. 

 

KV4.3 - Pharmacology of Metropolol Tartrate, using the CiPA Protocol

CiPA PE KV4.3 2icon sp96    SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV4.3 current traces in response to the CiPA voltage step protocol, measured on the SyncroPatch 384PE using the whole cell patch methodology and single-hole chips. The IC50 value of Metropolol Tartrate was determined as 128 µM.

 

 

CaV1.2 - Pharmacology of Nifedipine, using the CiPA protocol

icon sp96   CiPA PE CaV1 2 2SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hCaV1.2/β2/α2δ1 current traces in response to the CiPA voltage step protocol and the corresponing current-voltage relationship plot. Measured on the SyncroPatch 384PE using perforated patch methodology (Escin) and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 94%. The IC50 value of Nifedipine was determined as 106 nM.

 

hERG - Pharmacology using the CiPA Protocol

CiPA PE hERG Pharmacologyicon sp96   SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using whole cell patch clamp methodology and multi-hole chips (4 holes per well). The IC50 value of the following compounds of the peak current was determined as 4.18 µM for Diltiazem, 37.4 nM for Terfenadine, 971 nM for Quinidine, 63 µM for Mexiletine, 431 nM for Verapamil and 4.54 µM for Ranolazine. 

hERG - recordings with great stability using the CiPA step ramp protocol

CiPA PE hERG Pharmacology Stabilityicon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using perforated patch clamp methodology (Escin) and multi-hole chips (4 holes per well). 

Cardiac Ion Channels - Pharmacology of Sotalol

CiPA PE CE Pharmacology SotalolIcon CE    CardioExcyte 96 and   icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.

The image on the left hand side displays the results of the blocking effect of Sotalol on hERG. The result is in good agreement with manual patch clamp data (Crumb et al., 2016). The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 10 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility measurements.

KV4.3 - Pharmacology of Quinidine

CiPA PE Kv4 3icon sp96    SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV4.3 current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using the whole cell patch methodology and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was  95.3%. The IC50 value of Quinidine was determined as 21.2 µM (Literature: 79.3 µM, Crumb et al., J Pharmacol Toxicol Methods. 2016).

Kir2.1 - Pharmacology of Barium

CiPA PE Kir2 1icon sp96    SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing Kir2.1 current traces in response to a voltage step protocol. Measured on the SyncroPatch 384PE using the whole cell patch methodology and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was  93%. The IC50 value of Barium was determined as 6.38 µM (Literature: 16.2 µM, Schram et al. Cardiovasc Res. 2003).

KCa3.1 (SK4) - Activation by Perfusion of free internal Calcium

180209 Data PE SK4icon sp96    SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software are showing KCa3.1 raw traces and according time plots (online analysis) to a voltage ramp from -120 mV to + 60 mV over 200 ms. The application of internal Ca2+ is indicated by the yellow bar. The current increased upon application of internal Ca2+ reaching a peak within 1-2 min after the start of the perfusion. Five minutes of stable KCa3.1 current was recorded prior the channel was inhibited by cumulative additions of external Ba2+; first partly (1 mM Ba2+) and then completely (5 mM Ba2+). The recording was performed with perfectly high success rates in whole cell configuration on a multi hole chip (4 holes per well) using the SyncroPatch 384PE.

NaV1.9 - Pharmacology

NaV1.9 Dataset PE 1icon sp96    SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Icagen.

Screenshots of the PatchControl 384 software showing hNaV1.9 current traces in response to a voltage step protocol. Measured on the SyncroPatch 384PE using perforated patch methodology (Escin) and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was  86%. NaV1.9 is TTX insensitive. The IC50 value of lidocaine of the peak current was determined as 350 µM (Literature: 356 µM), the IC50 value of tetracaine of the peak current was determined as 12.5 µM (Literature: 32 µM).

NaV1.7 - Accurate Voltage Clamp

SyncroPatch 384PE Nav17 CHO Anaxon 384 raw IV 2

 icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Anaxon AG.

CHO cells expressing NaV1.7 were used on the SyncroPatch 384PE with a success rate of > 90% for cells which have a seal resistance > 500 MΩ (see inset). A screenshot of the PatchControl 384 software showing current traces in response to a voltage step protocol and the corresponding current-voltage plot.

GABAA Receptor (a1b3g2) - Antagonists

GABAa1 Antagonists

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Pharmacology on GABAA α1β3γ2 as recorded on a multihole (4x) plate. Mean concentration response curves for Bicuculline, IC50 = 470 nM (n = 14); for a5IA IC50 = 461.19 pM (n = 9), maximum block was 29% at 100 nM; for FG7142 IC50= 54.52 nM (n = 15), maximum block was 58% at 10 μM; for MRK016 maximum current inhibition was 44.8% at 1 uM, IC50= 5.98 nM (n = 11). 

GABAA Receptor (a1b3g2) - Bicuculline Dose Response

GABAa1 Bicuc DR vert

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Pharmacology on GABAA α1β3γ2 as recorded on a multihole (4x) plate. Raw data traces of one exemplary recording using control solution (A) and increasing Bicuculline concentrations and a subsequent  washout (B). Cells were held at a constant holding potential of -70 mV and GABA was applied for approximately 2 s. After 3 control applications of 3 μM GABA, increasing concentrations of inhibitors were applied. Cells were preincubated with antagonists before co-applicaiton with GABA. 

GABAA Receptor (a1b3g2) - Success Rates

Seal Stat GABAa1

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Statistic of hGABAA a1b3g2 cells recorded on one NPC-96 1-hole (1x) patch clamp chip. Cslow = 18.8 ±1.6 (n=32), Rs = 8.6 ± 1.5 (n=32). 41.66 % of the cells on one NPC-96 chip (total n=96) had seal resistance > 1 GOhm at the beginning and at the end of experiment. 63.4 % of the cells had a seal resistance above 500 MOhm, which remained stable throughout the experiment.

 

 

GABAA Receptor (a5b3g2) - Antagonists

GABAa5 Antagonists small

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Mean concentration response curves for Bicuculline, IC50 = 327 nM (n = 14); for a5IA IC50 = 933 pM (n = 11),  maximum block was 45% at 100 nM; for FG7142 IC50= 2.5 mM (n = 9), maximum block was 64.3% at 10 μM; for MRK016 maximum current inhibition was 52% at 1uM, IC50= 1.02 nM (n = 15).

GABAA Receptor (a5b3g2) - Dose Response

GABAa5 ver

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Pharmacology on GABAA α5β3γ2 as recorded on the SyncroPatch96. Raw data traces of one exemplary cell using increasing GABA concentrations (A) or increasing Bicuculline concentrations and a subsequent washout (B).

 

 

 

GABAA Receptor (a5b3g2) - Success Rates

Bar Seal cm Rs GABAa5AppNote

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Statistic of hGABAA α5β3γ2 cells recorded on one NPC-96 patch clamp chip. Cslow = 26.2 ±1.8 (n=32), Rs = 4.1 ± 0.2 (n=32). 53 % of the cells on one NPC-96 chip (total n=96) had seal resistance > 1 Giga Ohm at the beginning, 47 % at the end of experiment. 76 % of cells reached a seal resistance above 500 MΩ, which remained constant throughout the experiment.

 

 

 

NaV1.8 - Block by Tetracaine

Tet traces Conc responseicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

A Raw traces from an exemplar cell recorded on the SyncroPatch 96 showing inhibition of current by increasing concentrations of tetracaine. Shown are current responses to a single step protocol to 20 mV for 25 ms from a holding potential of -120 mV.
B Average concentration response curve for tetracaine, IC50 = 71 ± 5 μM (n = 40).

NaV1.8 - Block by Lidocaine

Lido traces ConcResponseicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

A Raw traces from an exemplar cell recorded on the SyncroPatch 96 showing inhibition of current by increasing concentrations of lidocaine. Shown are current responses to a single step protocol to 20 mV for 25 ms from a holding potential of -120 mV.
B Average concentration response curve for lidocaine, IC50 = 178 ± 11 μM (n = 35).

NaV1.8 - I/V Characteristics

ND723 Nav18 Syncro IV Figureicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications: 

The ND7-23 cells were kindly provided by Millipore.

A Raw traces from an exemplar cell recorded on the SyncroPatch 96. Shown are current responses to increasing voltage steps from -60 to +60 mV.
B Average current-voltage plot, Vhalf of activation was 12 mV (n = 32).
C Average inactivation plot, Vhalf of inactivation was -27 mV (n = 32). Nav1.8 currents started to activate at about -30 mV, peak response was elicited between 20 and 30 mV and Vhalf of activation was 12 mV. The Vhalf of inactivation was -27 mV in good agreement with the literature.

NaV1.7 - Success Rate & Access Resistance

SuccessRate Nav17 Rs Cm Syncroicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
The cells were kindly supplied by Millipore.

A Success rate (seal resistance) of ND7-23 cells on the SyncroPatch 96. Shown is a bar graph of seal resistances on the SyncroPatch 96 at the start (blue) and end (grey) of the experiment.
B Bar graph of cell capacitance (Cslow) of ND7-23 cells. Mean Cslow = 19.9 ± 0.8 pF (n = 75 ). 
C Bar graph of series resistance (Rs) values for ND7-23 cells on the SyncroPatch 96. Mean Rs = 9.1 ± 1.3 MΩ (n = 75).

NaV1.8 - Success Rate & Access Resistance

SuccessRate Seal cm Rs ND723 Syncroicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
The cells were kindly supplied by Millipore.

A Success rate (seal resistance) of ND7-23 cells on the SyncroPatch 96. Shown is a bar graph of seal resistances on the SyncroPatch 96 at the start (blue) and end (grey) of the experiment.
B Bar graph of cell capacitance (Cslow) of ND7-23 cells. Mean Cslow = 22.6 ± 0.8 pF (n = 88 ).
C Bar graph of series resistance (Rs) values for ND7-23 cells on the SyncroPatch 96. Mean Rs = 7.1 ± 0.4 MΩ (n = 88). 

 

TRPV1 - Activation by Internal Application of Capsaicin

0TRPV1 Internal Acticon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

The SyncroPatch 96 allows continues recording during the application of compounds from the intracellular side. Here, TRPV1 channels were activated by the internal application of capsaicin.

   

 

 

 

NaV1.5 - Analyzing iPSC-derived Cardiomyocytes

0NavLidocaineScreenicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly supplied by Cellular Dynamics.

Inhibition of NaV1.5 currents in stem cell-derived cardiomyocytes (iCells) by lidocaine. Lidocaine concentrations: 6 µM, 62 µM and 620 µM. The obatined  IC50 -value was 14 µM.

 

Acetylcholine Receptor Alpha 7 - Dose Response Curve

AChRCRCicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Galantos Pharma GmbH.

Increasing acetylcholine concentrations (30 µM, 100 µM and 300 µM) were added to the same cell using a stacked applications protocol. 

 

NaV1.5 - Blind Study using an Inactivation Protocol

NaInactivation

icon sp96   SyncroPatch data (a predecessor model of SyncroPatch 384PE) and applications:

22 selected compounds were tested in a blind study on the SyncroPatch 96 using HEK 293 cells expressing hNav1.5 ion channels. The IC50-values were compared to manual patch clamp measurements, performed at the customer site.

NaV1.5 - Lidocaine Dose Response

NaLidocaine

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Cytomyx Millipore

Timecourse of the NaV1.5 peak currents in response to exposure to different lidocaine concentrations (0 μM, 1 μM, 10 μM, 100 μM, 0 μM). Time points at which the external solution was exchanged is marked by the red lines.

NaV1.5 - Inactivation Protocol

NaInactivation

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Cytomyx Millipore.

Shown are raw current responses of HEK293 cells expressing hNaV1.5 to a double (inactivation) pulse protocol.

 

Erythrocytes - Analyzing Primary Cells

Erysicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Dr. Andrea Brüggemann.

Shown is a current recording from an erythrocytes as a response to a voltage ramp from -100 mV to +100 mV aquired on the SyncroPatch 96. The increase in current was induced by a reduction in osmoliarity.

 

NaV1.8 - Automated Analysis

DC96 overview CRCResults Nav18icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by EMD Millipore.

With the SyncroPatch Analysis Tool - DataControl96, IC50 plots are easily generated, displayed, averaged, evaluated, and modified.
Here, Lidocaine concentration response curves (CRC) of rNaV1.8 expressing ND7-23 cells are shown.

KV1.3 - Internal Perfusion

p41 1 IntPerficon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

The SyncroPatch 96 supports internal perfusion allowing internal administration of compounds, second messengers and metabolites. Here, KV1.3 currents, endogenously expressed in Jurkat cells, were blocked by the internal administration of Cs+ followed by washout with Cs+-free internal solution.

NMDA NR1/NR2A - Activation and Modulation

NMDA 384well view

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by B'Sys.

Here, activation and modulation of the NR1/NR2A subunit containing NMDA receptors are shown. Currents were evoked by application of 10 µM Glutamate in the presence of 10 µM Glycine.

Application of the neurosteroid Pregnenolone sulfate (PS) potentiates the current response induced by Glutamate. The potency of PS was analysed in a single-point screen. The EC50 of PS (39.6 µM), comprising 74% of the cells is nicely corresponding to litereature values (Irwin, et al. Neurosci. Lett. 1992)

Glycine Receptor (GlyRa1) - Reproducible Current Recordings

Glycine 384 raw OA reproducibleicon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:

Glycine-mediated current traces and corresponding time plots from 384 simultaneously recorded HEK cells are shown. Multiple additions of 50 µM Glycine produce very robust current responses with similar peaks, providing best conditions for cumulative pharmacology on one cell.

KV1.3 - Pharmacology with High Success Rate

Kv13 384 raw onl norm Quini 2icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Evotec.

Shown are screenshots of a pharmacology experiment performed with the SyncroPatch 384PE. Recordings from 384 KV1.3 expressing CHO cells were performed simultaneously. Original current traces and the peak current over time are displayed. Data are analysed with DataControl384 full analysis tool. With just a few mouse-clicks normalized concentration response curves can be generated. Here, normalized response and the IC50 of Quinidine is shown. Darkening shades of blue indicate increasing compound concentration.

hERG - Stable Recordings with Accurate Pharmacology

Syncro hERG 2icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications: 
Cells were kindly provided by Charles River Laboratories.

Current-voltage relationship of hERG (Kv11.1) expressed in HEK293 is shown along with pharmacology of 4 hERG-active compounds. The current-voltage relationships for all 384 wells (top) using perforated patch (Escin) and multi-hole chips (4 holes per well) are shown. In all 384 wells, a hERG-mediated current was observed with peak amplitude >700 pA at -20 mV. Using a pharmacology voltage protocol, experiments were stable lasting over 20 minutes. Concentration response curves for astemizole, pimozide, cisapride and terfenadine revealed IC50 values consistent with those found in the literature. 

AMPA Receptor (GluA2) - Current Traces

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by University of Sussex.

Using a stacked solutions approach and a fast pipetting speed shortens the solution exchange rate and minimizes the ligand exposure time. This procedure allows for reproducible recordings of fast desensitizing ligand-gated receptors such as glutamate receptors.
Here, repetitive activation of GluA2 receptors is shown. Receptors were activated with 100 µM Na-Glutamate for 3 times resulting in inward currents of similar peak amplitudes (A and B). The current onset time was approximately 10 ms (D). Panel C displays an example of a cumulative concentration response curve for Na-Glutamate (in mM: 0.1, 0.3 and 1).

TRPV1 - Application of Capsaicin

TRPV1 bea verzerrticon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

Using the SyncroPatch 96 CHO cells expressing TRPV1 were subjected to a voltage ramp (-100 mV to +100 mV) in the presence and absence (control) of 2 μM capsaicin. As shown in the exemplar traces, inward and outward currents increase upon capsaicin addition.

GABAA Receptor - Modulator Diazepam

Diazepam

 icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

Shown is a raw current response of a HEK293 cell expressing GABAA receptors to initial exposure to GABA, followed by joint exposure to GABA and diazepam (as indicated). Solutions were  stacked (layered) in the pipette to achieve brief exposure times.

Acetylcholine Receptor Alpha 3 Beta 4 - Activation

a3b4

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

Shown is a raw current response of a HEK293 cell expressing AChR (α3β4) to exposure to 300 μM nicotine. Solutions were  stacked (layered) in the pipette to achieve brief exposure times.

 

GABAA Receptor (a1b2g2) - On-set of response

Gaba and close up bea

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

With the SyncroPatch 96 currents can be recorded continuously during compound application. This, in conjunction with a solution exchange time of about 100 ms, makes the SyncroPatch 96 an excellent tool for investigations of ligand gated ion channels. In the data example, 10 μM GABA was added to a HEK293 cell expressing GABAA (α1β2γ2) receptors. The boxed trace shows a close up of the GABA-response.

NaV1.5 - Current Voltage Relationship

NaStrom IV

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Millipore.

Borosilicate glass chips are used as the patch clamp substrate, ensuring excellent voltage clamp of the cell membrane and high quality seals. Voltage gated channels such as hNaV1.5 (HEK293) have been used to validate the system. This data example shows the I/V characteristics and the corresponding raw current traces of a single cell from a recording on the SyncroPatch 96.

 

 

CaV1.2 - Current Voltage Relationship

Cav12 IV

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

Shown are raw current traces (top) and the constructed peak current-voltage relationship (bottom) of CaV1.2 (HEK293) recorded on the SyncroPatch 96.

 

 

 

 

 

hERG - Current Voltage Relationship

HergIV No and with Leak

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Cytomyx Millipore.

Borosilicate glass chips are used as the patch clamp substrate, ensuring excellent voltage control of the cell membrane and high quality seals. Voltage gated channels such as hERG (expressed in HEK293) have been used to validate the system. These traces show the raw current responses of a single cell to a hERG IV pulse protocol. The data were recorded on the SyncroPatch 96. In the upper screenshot raw current traces are shown. In the lower one the same current traces after leak subtraction are shown.

 

 

KV7.1 (KVLQT) - Dose-response curve

icon sp96   170922 KV7.1 Data SyncroPatch384PESyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV7.1/KCNE (KVLQT/minK) current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Using the perforated patch methodology (Escin) in combination with multi-hole chips (4 holes per well), stably transfected cells were measured on the SyncroPatch 384PE. The IC50 value of Chromanol 293B was determined as 3.82 µM. The success rate of valuable data for the analysis was 100%. 

KV4.3/KChIP2 - Dose-response curve of Flecanaide

icon sp96   170922 KV4.3 Data SyncroPatch384PESyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV4.3/KChIP2 current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Using whole cell mode in combination with multi-hole chips (4 holes per well), stably transfected cells were measured on the SyncroPatch 384PE. The IC50 value of flecainide was determined as 28.3 µM which is in accordance to literature. The success rate of valuable data for the analysis was 100%. 

CaV1.2 - Stable recording from frozen stock cells

icon sp96   170922 CaV1.2 Data SyncroPatch384PESyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hCaV1.2β2/α2δ1 current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Measured on the SyncroPatch 384PE using perforated patch methodology (Escin) and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 100 %. The cells were used from a frozen cell stock (after induction) and recorded stably for more than 20 minutes. The IC50 value of Nifedipine was determined as 21 nM.

KV1.5 - Dose response curve of 4-AP

icon sp96   KV1.5 Data 3845PESyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing a dose-response curve of 4-AP on KV1.5 stably transfected cells. Measured on the SyncroPatch 384PE using multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 100%. The IC50 value of 160 µM measured on the SyncroPatch 384PE corresponds well to literature (IC50 4-AP: 270 µM; Gutman et al., Pharmacological Reviews 57: 473-508, 2005). 

Publications

2020 - VU0606170, a Selective Slack Channels Inhibitor, Decreases Calcium Oscillations in Cultured Cortical Neurons

icon sp96  SyncroPatch 768 PE publication in ACS Chemical Neuroscience (2020)

Authors:
Spitznagel B.D., Mishra N.M., Qunies A.M., Prael F.J., Du Y., Kozek K.A., Lazarenko R.M., Denton J.S., Emmitte K.A., Weaver C.D.

2020 - Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk

 icon sp96 SyncroPatch 384 (a predecessor model of the SyncroPatch 768i instrument) publication in Cell Stem Medicine (2020)

Authors:
Davies M.R., Martinec M., Walls R., Schwarz R., Mirams G.R., Wang K., Steiner G., Surinach A., Flores C., Lave T., Singer T., Polonchuk L.

2020 - Trends in the Development of Diagnostic Tools for Red Blood Cell-Related Diseases and Anemias

 icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) publication in Frontiers in Physiology (2020)

Authors:
Kaestner L., Bianchi P.

2020 - Striatal Kir2 K+ channel inhibition mediates the antidyskinetic effects of amantadine

 icon sp96   SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i instrument) publication in The Journal of Clinical Investigation (2020)

Authors:
Shen W., Ren W., Zhai S., Yang B., Vanoye C.G., Mitra A., George AL. Jr., Surmeier D.J.

2020 - Reliable identification of cardiac liability in drug discovery using automated patch clamp: Benchmarking best practices and calibration standards for improved proarrhythmic assessment

icon pl   Patchliner and   icon sp96   SyncroPatch 384i (SyncroPatch 384PEa predecessor model) publication in the Journal of Pharmacological and Toxicological Methods (2020)

Authors:
Brinkwirth N., Takasuna K., Masafumi D., Becker N., Obergrussberger A., Friis S., Furukawa Y., Hasegawa Y., Oka T., Ohtsuki A., Fertig N., Stoelzle-Feix S.

2020 - Reengineering an Antiarrhythmic Drug Using Patient hiPSC Cardiomyocytes to Improve Therapeutic Potential and Reduce Toxicity

icon pl Patchliner and  icon sp96 SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i instrument) publication in Cell Stem Cell (2020)

Authors:
McKeithan W. L., Feyen D.A.M., Bruyneel A.A.N., Okolotowicz K.J., Ryan D.A., Sampson K.J., Potet F., Savchenko A., Gómez-Galeno J., Vu M., Serrano R., George Jr. A.L., Kass R.S., Cashman J.R., Mercola M.

2020 - Novel Expression of GABAA Receptors on Resistance Arteries That Modulate Myogenic Tone

icon sp96   SyncroPatch 96 (a predecessor model of the SyncroPatch 384i) Publication in Journal of Vascular Research (2020)

Authors:
Yim P.D., Gallos G., Lee-Kong S.A., Dan W., Wu A.D., Xu D., Berkowitz D.E., Emala C.W.

2020 - Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization

 icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) pre-publication in bioRxiv (2020)

Authors:
Matsumura K., Shimomura T., Kubo Y., Oka T., Kobayashi N., Imai S., Yanase N., Akimoto M., Fukuda M., Yokogawa M., Ikeda K., Kurita J., Nishimura Y., Shimada I., Osawa M.

2020 - Mechanism and site of action of big dynorphin on ASIC1a

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Publication in PNAS (2020)

Authors:
Borg C.B., Braun N., Heusser S.A., Bay Y., Weis D., Galleano I., Lund C., Tian W., Haugaard-Kedström L.M., Bennett E.P., Lynagh T., Strømgaard K., Andersen J., Pless S.A.

2020 - Ion Channels and Relevant Drug Screening Approaches

icon sp96   SyncroPatch 384i editorial found in SLAS Discovery (2020)

Authors:
McGivern, J.G., Ding M.

2020 - High-throughput reclassification of SCN5A variants

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Publication in The American Journal of Human Genetics (2020)

Authors:
Glazer A.M., Wada Y., Li B., Muhammad A., Kalash O.R., O’Neill M.J., Shields T., Hall L., Short L., Blair M.A., Kroncke B.M., Capra J.A., Roden D.M

2020 - High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel KCNH2: Deep mutational scan of KCNH2 trafficking

 icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) Pre-publication in bioRxiv Biology (2020)

Authors:
Kozek K.A., Glazer A.M., Ng C.-A., Blackwell D., Egly C.L., Vanags L.R., Blair M., Mitchell D., Matreyek K.A., Fowler D.M., Knollmann B.C., Vandenberg J., Roden D.M., Kroncke B.M.

2020 - GS-967 and Eleclazine Block Sodium Channels in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i) pre-publication in bioRxiv (2020)

Authors:
Potet F., Egecioglu D.E., Burridge P.W.,George A.L. Jr.

2020 - Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i instrument) publication in Medicinal Chemistry (2020)

Authors:
Scott J.S., Moss T.A., Balazs A., Barlaam B., Breed J., Carbajo R.J., Chiarparin E., Davey P.R.J., Delpuech O., Fawell S., Fisher D.I., Gagrica S., Gangl E.T., Grebe T., Greenwood R.D., Hande S., Hatoum-Mokdad H., Herlihy K., Hughes S., Hunt T.A., Huynh H., Janbon S.L.M., Johnson T., Kavanagh S., Klinowska T., Lawson M., Lister A.S., Marden S., McGinnity D.F., Morrow C.J., Nissink W.M., O'Donovan D.H., Peng B., Polanski R., Stead D.S., Stokes S., Thakur K., Throner S.R., Tucker M.J., Varnes J., Wang H., Wilson D.M., Wu D., Wu Y., Yang B., Yang W.

2020 - Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells

icon pl   Patchliner and   icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) publication in Nature Scientific Reports (2020)

Authors:
Kramer J., Himmel H.M., Lindqvist A., Stoelzle-Feix S., Chaudhary K.W., Li D., Bohme G.A., Bridgland-Taylor M., Hebeisen S., Fan J., Renganathan M., Imredy J., Humphries E.S.A, Brinkwirth N., Strassmaier T., Ohtsuki A., Danker T., Vanoye C., Polonchuk L., Fermini B., Pierson J.B. & Gintant G.

2020 - Conservation and divergence in NaChBac and NaV1.7 pharmacology reveals novel drug interaction mechanisms

 icon sp96   SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i instrument) publication in Nature Scientific Reports (2020)

Authors:

Zhu W., Li T., Silva J. R., Chen J.

2020 - Computer modeling of whole-cell voltage-clamp analyses to delineate guidelines for good practice of manual and automated patch-clamp

 icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) pre-publication in BioRxiv (2020)

Authors:
Montnach J., Lorenzini M., Lesage A., Simon I., Nicolas S., Moreau E., Marionneau C., Baró I., De Waard M., Loussouar G.

2020 - Automated Patch Clamp in Drug Discovery: major breakthroughs and innovation in the last decade

 icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument)   icon pl   Patchliner and   icon pap   Port-a-Patch publication in Expert Opinion on Drug Discovery (2020)

Authors:
Obergrussberger A., Friis S., Brüggemann A., Fertig N.

2020 - Application of High-Throughput Automated Patch-Clamp Electrophysiology to Study Voltage-Gated Ion Channel Function in Primary Cortical Cultures

 icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in SLAS Discovery (2020)

Authors:
Toh M.F., Brooks J.M., Strassmaier T., Haedo R.J., Puryear C.B., Roth B.L., Ouk K., Pin S.S.

2020 - Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) publication in Philosophical Transactions of the Royal Society A (2020)

Authors:
Lei, C.L., Clerx, M., Whittaker, D.G., Gavaghan, D.J., de Boer, T.P., Mirams, G.R.

2020 - A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm

icon pl   Patchliner and   icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) publication in Toxicology and Applied Pharmacology (2020)

Authors:
Ridder B.J., Leishman D.J., Bridgland-Taylor M., Samieegohar M., Han X, Wu W.W., Randolph A., Tran P., Sheng J., Danker T., Lindqvist A., Konrad D., Hebeisen S., Polonchuk L., Gissinger E., Renganathan M., Koci B., Wei H., Fan J., Levesque P., Kwagh J., Imredy J., Zhai J., Rogers M., Humphries E., Kirby R., Stoelzle-Feix S., Brinkwirth N., Rotordam M.G., Becker N., Friis S., Rapedius M., Goetze T.A., Strassmaier T., Okeyo G., Kramer J., Kuryshev Y., Wu C., Himmel H., Mirams G.R., Strauss D.G., Bardenet R., Li Z.

2020 - A general procedure to select calibration drugs for lab-specific validation and calibration of proarrhythmia risk prediction models: An illustrative example using the CiPA model

 icon sp96   SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i instrument) publication in the Journal of Pharmacological and Toxicological Methods (2020)

Authors:

Han X., Samieegohar M., Ridder B.J., Wu W.W., Randolph A., Tran P., Sheng J., Stoelzle-Feiz S., Brinkwirth N., Rotordam M.G., Becker N., Friis S., Rapedius M., Goteze T.A., Strassmaier T., Okeyo G., Kramer J., Kuryshev Y., Li Z.

2019 - Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Bioorganic & Medicinal Chemistry (2019)

Authors:
Zoukimian C., Meudal H., De Waard S., Ait Quares K., Nicolas S., Canepari M., Béroud R., Landon C., De Waard M., Boturyn D.

2019 - Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Medicinal Chemistry (2019)

Authors:
McKerrall S.J., Nguyen T., Lai K.W., Bergeron P., Deng L., DiPasquale A., Chang J.H., Chen J., Chernov-Rogan T., Hackos D.H., Maher J., Ortwine D.F., Pang J., Payandeh J., Proctor W.R., Shields S.D., Vogt J., Ji P., Liu W., Ballini E., Schumann L., Tarozzo G., Bankar G., Chowdhury S., Hasan A., Johnson J.P. Jr., Khakh K., Lin S., Cohen C.J., Dehnhardt C.M., Safina B.S., Sutherlin D.P.

2019 - Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Cell (2019)

Authors:
Xu H., Li T., Rohou A., Arthur C.P., Tzakoniati F., Wong E., Estevez A., Kugel C., Franke Y., Chen J., Ciferri C., Hackos D.H., Koth C.M., Payandeh J.

2019 - Spectrum of KV2.1 Dysfunction in KCNB1‐Associated Neurodevelopmental Disorders

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) Publication Annals of Neurology (2019)

Authors: 
Kang, S.K., Vanoye, C.G., Misra, S.N., Echevarria, D.M., Calhoun, J.D., O’Connor, J.B., Fabre, K.L., McKnight, D., Demmer, L., Goldenberg, P., Grote, L.E., Thiffault, I., Saunders, C., Strauss, K.A., Torkamani, A., van der Smagt, J., van Gassen, K., Carson, R.P., Diaz, J., Leon, E., Jacher, J.E., Hannibal, M.C., Litwin, J., Friedman, N.R., Schreiber, A., Lynch, B., Poduri, A., Marsh, E.D., Goldberg, E.M., Millichap, J.J., George Jr., A.L., Kearney, J.A.

2019 - Role of High‐Throughput Electrophysiology in Drug Discovery

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i),   icon pl   Patchliner and   icon pap   Port-a-Patch review article in Current Protocols in Pharmacology (2019)

Authors:
Liu C., Li T., Chen J.

2019 - Rapid characterisation of hERG channel kinetics II: temperature dependence

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Biophysical Journal (2019)

Authors:
Lei C.L., Clerx M., Beattie K.A., Melgari D., Hancox J.C., Gavaghan D.J., Polonchuk L., Wang K., Mirams G.R.

2019 - Rapid characterisation of hERG channel kinetics I: using an automated high-throughput system

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Biophysical Journal (2019)

Authors:
Lei C.L., Clerx M., Beattie K.A., Gavaghan D.J., Polonchuk L., Mirams G.R., Wang K.

2019 - Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Pre-publication in bioRxiv Biology (2019)

Authors:
Heyne H.O., Baez-Nieto D., Iqbal S., Palmer D., Brunklaus A., Johannesen K.M., Lauxmann S., Lemke J.R., Møller R.S., Pérez-Palma E., Scholl U., Syrbe S., Lerche H., May P., Lal D., Campbell A.J., Pan J., Wang H.-R., Daly M.J.

2019 - Pharmacological activation of IKr in models of long QT Type 2 risks overcorrection of repolarization

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Cardiovascular Research (2019)

Authors:
Perry M.D., Ng C-A., Mangala M.M., Ng T.Y.M., Hines A.D., Liang W., Xu M.J.O., Hill A.P., Vandenberg J.I.

2019 - In vitro and in vivo characterization of a synthetic scorpion toxin AmmTx3, a potent inhibitor of cardiac voltage-gated potassium channel Kv4.2

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) publication in Archives of Cardiovascular Diseases Supplements (2019)

Authors:
Nicolas S., Zoukimian C.,Meuda H., De Waard S., Ait Ouares K., Canepari M., Beroud R., Landon C., De Waard M., Boturyn D.

2019 - High-throughput phenotyping of heteromeric human ether-à-go-go-related gene potassium channel variants can discriminate pathogenic from rare benign variants

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Heart Rhythm (2019)

Authors:
Ng C-A., Perry M.D., Liang W., Smith N.J., Foo B., Shrier A., Lukacs G.L., Hill A.P., Vandenberg J.I.

2019 - High Throughput Characterization of KCNB1 Variants Associated with Developmental and Epileptic Encephalopathy

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) Pre-publication in bioRxiv (2019)

Authors: 
Kang, S.K., Vanoye, C.G., Misra, S.N., Echevarria, D.M., Calhoun, J.D., O’Connor, J.B., Fabre, K.L., McKnight, D., Demmer, L., Goldenberg, P., Grote, L.E., Thiffault, I., Saunders, C., Strauss, K.A., Torkamani, A., van der Smagt, J., van Gassen, K., Carson, R.P., Diaz, J., Leon, E., Jacher, J.E., Hannibal, M.C., Litwin, J., Friedman, N.R., Schreiber, A., Lynch, B., Poduri, A., Marsh, E.D., Goldberg, E.M., Millichap, J.J., George Jr., A.L., Kearney, J.A.

2019 - Functional consequences of a KCNT1 variant associated with status dystonicus and early‐onset infantile encephalopathy

icon sp96   SyncroPatch 384PE (a predeccessor model of the SyncroPatch 384i) publication in Annals of Clinical and Translational Neurology (2019)

Authors:
Gertler T.S., Thompson C.H., Vanoye C.G., Millichap J.J., George Jr A.L.

2019 - Electrophysiological evaluation of pentamidine and 17-AAG in human stem cell-derived cardiomyocytes for safety assessment

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) article in European Journal of Pharmacology (2019)

Authors:
Asahi Y., Nomura F., Abe Y., Doi M., Sakakura T., Takasuna K., Yasuda K.

2019 - Development of Photocrosslinking Probes Based on Huwentoxin-IV to Map the Site of Interaction on Nav1.7

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) Publication in Cell Chemical Biology (2019)

Authors: 
Tzakoniati F., Xu H., Li T., Garcia N., Kugel C., Payandeh J., Koth C.M., Tate E.W.

2019 - Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) article in Bioorganic and Medicinal Chemistry Letters (2019)

Authors:
Sharma, S.H., Pablo J.L., Montesinos, M.S., Greka, A., Hopkins, C.R.

2019 - Compounds commonly used in equine medicine inhibits the voltage-gated potassium channel Kv11.1

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Research in Veterinary Science (2019)

Authors:
Calloe K., Rognant, S., Friis S., Shaughnessy C., Klaerke D.A., Trachsel D.

2019 - Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1

icon sp96  SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) publication in Toxins (2019)

Authors: 
Nicolas S., Zoukimian C., Bosmans F., Montnach J., Diochot S., Cuypers E., De Waard S., Béroud R., Mebs D., Craik D., Boturyn D., Lazdunski M., Tytgat J., De Waard M.

2019 - Aptamer Efficacies for In Vitro and In Vivo Modulation of αC-Conotoxin PrXA Pharmacology

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Molecules (2019)

Authors:
Taiwe G.S., Montnach J., Nicolas S., De Waard S., Fiore E., Peyrin E., El-Aziz T.M.A., Amar M., Molgó J., Ronjat M., Servent D., Ravelet C., De Waard M.

2019 - A Novel Gain-Of-Function Mutation Of Piezo1 Is Functionally Affirmed In Red Blood Cells By High-Throughput Patch Clamp

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Haematologica (2019)

Authors:
Rotordam G.M., Fermo E., Becker N., Barcellini W., Brüggemann A., Fertig N., Egée S., Rapedius M., Bianchi P., Kaestner L.

2018 - Towards Novel Bioactive Antiperspirants for Cosmetic Applications

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in IFSCC (2018)

Authors:
Ertongur-Fauth T., Fischer S., Hartmann D., Brüggemann A., Seeger V., Kleber A., Krohn M.

2018 - NaV Channels: Assaying Biosynthesis, Trafficking, Function

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) article in The Surfaceome (2018)

Authors:
Tomaselli G.F., Farinelli F.

2018 - Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D)

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) -related publication in International Journal of Cardiology (2018)

Authors:
Calloe K., Broendberg A.K., Christensen A.H., Pedersen L.N., Olesen M.S., de los Angeles Tejada M., Friis S., Thomsen M.B., Bundgaard H., Jensen H.K.

2018 - Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) publication in PNAS

Authors: 
Chernov-Rogan T., Li T., Lu G., Verschoof H., Khakh K., Jones S.W., Beresini M.H., Liu C., Ortwine D.F., McKerrall S.J., Hackos D.H., Sutherlin D., Cohen C.J., and Chen J.

2018 - High-Throughput Functional Evaluation of KCNQ1 Decrypts Variants of Unknown Significance

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) article in Circulation: Genomic and Precision Medicine (2018)

Authors:
Vanoye C.G., Desai R.R., Fabre K.L., Gallagher S.L., Potet F., DeKeyser J.M., Macaya D., Meiler J, Sanders C.R, and George Jr. A.L.

2018 - Developing High-Throughput Assays to Analyze and Screen Electrophysiological Phenotypes

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) book chapter in Phenotypic Screening (2018)

Authors:
Pan J.Q., Baez-Nieto D., Allen A., Wang HR., Cottrell J.R.

2018 - An update on the advancing high-throughput screening techniques for patch clamp-based ion channel screens: implications for drug discovery

icon sp96   SyncroPatch 384/768PE (a predecessor model of SyncroPatch 384/768i) and   icon pl   Patchliner publication in Expert Opinion on Drug Discovery

Authors: 
Obergrussberger A., Goetze T.A., Brinkwirth N., Becker N., Friis S., Rapedius M., Haarmann C., Rinke-Weiß I., Stölzle-Feix S., Brüggemann A., George M., Fertig N.

2017 - Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions

icon sp96  SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in Nature Communications (2017)

Authors: 
Chiang E.Y., Li T., Jeet S., Peng I., Zhang J., Lee W. P., DeVoss J., Caplazi P., Chen J., Warming S., Hackos D.H., Mukund S., Koth C.M., Grogan J.L.

2017 - High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE

icon sp96  SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in PLoS One (2017)

Authors: 
Li T, Lu G, Chiang E.Y., Chernov-Rogan T., Grogan J.L., Chen J.

2017 - Characterization of a KCNB1 variant associated with autism, intellectual disability, and epilepsy

icon sp96  SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in Neurology Genetics (2017)

Authors: 
Calhoun, J.D., Vanoye, C.G., Kok, F., George, A.L., Kearney, J.A.

2017 - Automated Patch Clamp Recordings of Human Stem Cell- Derived Cardiomyocytes.

icon pl  Patchliner and   icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) book chapter in Stem Cell-Derived Models in Toxicology (2017)

Authors: 
Obergrussberger A., Haarmann C., Stölzle-Feix S., Becker N., OhtsukiA., Brüggemann A., George M., Fertig N.

2016 - Use-dependent Block of Human Cardiac Sodium Channels by GS967

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Molecular Pharmacology (2016)

Authors: 
Potet F., Vanoye C.G., George Jr. A.L.

2016 - pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Biochimica et Biophysica Acta (2016)

Authors: 
Sauter D.R.P., Sørensen C.E., Rapedius M., Brüggemann A., Novak I.

2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Lab Automation (2016)

Authors: 
Obergrussberger A., Brüggemann A., Goetze T.A., Rapedius M., Haarmann C., Rinke I., Becker N., Oka T., Ohtsuki A., Stengel T., Vogel M., Steindl J., Mueller M., Stiehler J., George M., Fertig N.

2015 - Novel screening techniques for ion channel targeting drugs

icon pl  Patchliner,   icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and   Icon CE   CardioExcyte 96 publication in Channels (2015)

Authors: 
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.

2015 - Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in BCM Pharmacology and Toxicology (2015) 

Authors: 
Haraguchi Y., Ohtsuki A., Oka T., Shimizu T.

2014 - New strategies in ion channel screening for drug discovery: are there ways to improve its productivity?

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Laboratory Automation (2014)

Authors: 
Farre C., Fertig N.

2014 - Early identification of hERG liability in drug discovery programs by automated patch clamp

icon pl  Patchliner and   icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Frontiers in Pharmacology (2014)

Authors: 
Danker T., Moeller C.

2012 - Natural and artificial ion channels for biosensing platforms

icon pap   Port-a-Patch,   icon pl   Patchliner,   icon sp96   SyncroPatch 96 ((a predecessor model of SyncroPatch 384PE) and   icon vpp   Vesicle Prep Pro publication in Analytical and Bioanalytical Chemistry (2012)

Authors: 
Steller L., Kreir M., Salzer R.

2012 - HTS techniques for patch clamp-based ion channel screening - economy and advances

icon pap   Port-a-Patch,   icon pl   Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Expert Opinion on Drug Discovery (2012)

Authors: 
Farre C. and Fertig N.

2011 - State-of-the-art automated patch clamp devices: heat activation, action potentials, and high throughput in ion channel screening

icon pap   Port-a-Patch,   icon pl  Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)

Authors: 
Stoelzle S., Obergrussberger A., Brüggemann A., Haarmann C., George M., Kettenhofen R., Fertig N.

2011 - Automated electrophysiology makes the pace for cardiac ion channel safety screening

icon pl  Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)

Authors: 
Möller C., Witchel H.

2010 - Renaissance of ion channel research and drug discovery by patch clamp automation

icon pap  Port-a-Patch,   icon pl   Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE)  publication in Future Medical Chemistry (2010)

Authors:
Farre C. and Fertig N.

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