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 - 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).

NaV1.7 - 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.

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

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.

Publications

 

 

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