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
SyncroPatch 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).
NaV1.7 - Frequency Dependent Inhibition
SyncroPatch 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 - Accurate Voltage Clamp
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.
NaV1.7 - Success Rate & Access Resistance
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"
SyncroPatch 96 application note, (a predecessor model of the SyncroPatch 384PE) 
(0.6 MB)
Cells were kindly provided by Millipore.
NaV1.7 - "Pharmacology on hNaV1.7 performed on Nanion’s Patchliner at Vhalf "
Patchliner application note: (0.4 MB)
Cells were kindly provided by Anaxon.
NaV1.7 - "Patch clamp recordings of hNaV1.7 on Nanion’s Port-a-Patch"
Port-a-Patch application note (0.7 MB)
Cells were kindly provided by Anaxon
NaV1.7 - "Characterization of hNaV1.7 on Nanion's SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (0.7 MB)
Cells were kindly provided by Anaxon.
Webinars & Movies
28.04.2020 | Webinar: Validation and optimization of automated patch clamp voltage-gated Ca2+ channel assays
Patchliner Webinar
Date: April 28. 2020, 4:00 PM CET (10:00 AM EDT)
Marc will outline the development, optimization and validation of a range of voltage-gated Ca2+ channel assays on the Patchliner automated patch clamp platform that were subsequently used in an 8 year drug discovery collaboration between Metrion Biosciences and a german pharma company.
Speakers:
Dr. Marc Rogers (Chief Scientific Officer, Metrion Biosciences)
Dr. András Horváth (Application Scientist, Nanion Technologies)
03.11.2016 | External Webinar: Accelerating Ion Channel Characterization and New Drug Candidate Identification
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i)
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
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Oral Presentation Video
Presenter:
Dr. Markus Rapedius, Senior Scientist, Nanion Technologies
Posters
2018 - Investigating pain pathways by inhibition of voltage-gated sodium channels
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) and Patchliner poster, FENS Meeting 2018 (2.5 MB)
2017 - Cardiomyocytes in Voltage Clamp and Current Clamp by Automated Patch Clamp
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and Patchliner poster, BPS Meeting 2017 (1.7 MB)
Publications
2019 - Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain
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
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 - Fenamates inhibit human sodium channel Nav1.7 and Nav1.8
Port-a-Patch publication in Neuroscience Letters (2019)
Authors:
Sun, J-F., Xu, Y-J., Kong, X-H., Su, Y., Wang, Z-Y.
2019 - Development of Photocrosslinking Probes Based on Huwentoxin-IV to Map the Site of Interaction on Nav1.7
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 - Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1
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.
2018 - The opioid oxycodone use‐dependently inhibits the cardiac sodium channel Nav1.5
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
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.
2017 - High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE
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 - A mutant of the Buthus martensii Karsch antitumor-analgesic peptide exhibits reduced inhibition to hNav1.4 and hNav1.5 channels while retaining analgesic activity
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
Port-a-Patch and 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
Port-a-Patch publication in Biochemical Pharmacology (2012)
Authors:
Vetter I., Dekan Z., Knapp O., Adams D.J., Alewood P.F., Lewis R.J.