NaV1.7| sodium voltage-gated channel alpha subunit 9

Family:
Sodium channels

Subgroups:
NaV1.1-1.9

Topology:
Alpha subunits consist of four homologous domains (I-IV) with six transmembrane alpha helices (S1–S6) and a pore-forming loop. One a subunit may associate with 1 or 2 b subunits to make up the channel.

NaV1.7: Background Information

NaV1.7 is a voltage-gated sodium channel and plays a critical role in the generation and conduction of action potentials and is thus important for electrical signaling by most excitable cells. The NaV1.7 channel produces a rapidly activating and inactivating current which is sensitive to the level of tetrodotoxin. It is usually expressed at high levels in two types of neurons, the nociceptive (pain) neurons at dorsal root ganglion (DRG) and trigeminal ganglion, and sympathetic ganglion neurons, which are part of the autonomic (involuntary) nervous system.

Gene:
SCN9A

Human Protein:
UniProt Q15858

Tissue:
Sensory neurons, smooth myocytes, myenteric neurons, erythroid progenitor cells, immune cells, Schwann cells

Function/ Application:
Nociception signalling, sensory neuron excitability

Pathology:
Erythermalgia (IEM, PERYTHM), pain (CIP, PEPD), anosmia, epilepsy (GEFSP7), cancer

Accessory subunits:
b1, b2

Interaction:
NGF, NEDD4, NEDD4L, calmodulin

Modulator:
Tetrodotoxin, α-scorpion toxin, lidocaine

Assays:
Patch Clamp: whole cell, room temperature, State- and use-dependence

Particularities:
NaV channel analysis requires GigaOhm seals and a stable and low access resistance

Recommended Reviews:
International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacol Rev 57: 397–409, Catterall, et al. 2005 

Data and Applications

NaV1.7 - Pharmacology of Lidocaine

icon sp96   PE NaV1.7 LidocaineSyncroPatch 384PE 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).

NaV1.7 - Frequency Dependent Inhibition

icon sp96   PE NaV1.7 TetracaineSyncroPatch 384PE 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 - Accurate Voltage Clamp

SyncroPatch 384PE Nav17 CHO Anaxon 384 raw IV 2

 icon sp96   SyncroPatch 384PE 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.

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).

Application Notes

NaV1.7 - "Pharmacology on rNaV1.7 performed on Nanion‘s SyncroPatch 96"

icon sp96   SyncroPatch 96 application note, (a predecessor model of the SyncroPatch 384PE)   logo pdf   (0.6 MB)
Cells were kindly provided by Millipore.

NaV1.7 - "Pharmacology on hNaV1.7 performed on Nanion’s Patchliner at Vhalf "

icon pl   Patchliner application note:   logo pdf   (0.4 MB)
Cells were kindly provided by Anaxon.

NaV1.7 - "Patch clamp recordings of hNaV1.7 on Nanion’s Port-a-Patch"

icon pap   Port-a-Patch application note   logo pdf   (0.7 MB)
Cells were kindly provided by Anaxon

NaV1.7 - "Characterization of hNaV1.7 on Nanion's SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (0.7 MB)
Cells were kindly provided by Anaxon.

Webinars & Movies

03.11.2016 | External Webinar: Accelerating Ion Channel Characterization and New Drug Candidate Identification

icon sp96   SyncroPatch 384PE

This webinar will show high-throughput functional annotation of human ion channel variants associated with excitation disorders will be described along with use of the Syncropatch 384PE to measure subtype selective activation of KV7 potassium channels as well as inhibition of voltage gated sodium channels like NaV1.7, NaV1.1, and NaV1.5.
Organisation: Icagen Inc.

2018 - Biophysical and Pharmacological Characterization of Voltage-Gated Sodium Channels Involved in Pain Pathways

icon sp96   SyncroPatch 384PE Oral Presentation Video

Presenter: 
Dr. Markus Rapedius, Senior Scientist, Nanion Technologies

Posters

2018 - Investigating pain pathways by inhibition of voltage-gated sodium channels

icon sp96   SyncroPatch 384PE and   icon pl   Patchliner poster, FENS Meeting 2018  logo pdf   (2.5 MB)

2017 - Cardiomyocytes in Voltage Clamp and Current Clamp by Automated Patch Clamp

icon sp96   SyncroPatch 384PE and   icon pl   Patchliner poster, BPS Meeting 2017  logo pdf   (1.7 MB)

Publications

2018 - The opioid oxycodone use‐dependently inhibits the cardiac sodium channel Nav1.5

Icon CE   CardioExcyte 96 publication in British Journal of Pharmacology (2018)

Authors:
Meents J.E., Juhasz K., Stölzle-Feix S., Peuckmann-Post V., Rolke R. Lampert A.

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

icon sp96  SyncroPatch 768PE 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.

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

icon sp96  SyncroPatch 768PE publication in PLoS One (2017)

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

2017 - A mutant of the Buthus martensii Karsch antitumor-analgesic peptide exhibits reduced inhibition to hNav1.4 and hNav1.5 channels while retaining analgesic activity

icon pap   Port-a-Patch publication in Journal of Biological Chemistry (2017)

Authors:
Xu Y., Meng X., Hou X., Sun J., Kong X., Sun Y., Liu Z., Ma Y., Niu Y., Song Y., Cui Y., Zhao M., Zhang J.

2014 - Automated Patch Clamp Analysis of nAChα7 and NaV1.7 Channels

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Current Protocols in Pharmacology (2014)

Authors: 
Obergrussberger A., Haarmann C., Rinke I., Becker N., Guinot D., Brueggemann A., Stoelzle-Feix S., George M., Fertig N.

2012 - Isolation, characterization and total regioselective synthesis of the novel μO-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels

icon pap   Port-a-Patch publication in Biochemical Pharmacology (2012)

Authors: 
Vetter I., Dekan Z., Knapp O., Adams D.J., Alewood P.F., Lewis R.J.

 

 

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