NaV1.3 | sodium voltage-gated channel alpha subunit 3

Family:
Sodium channels

Subgroups:
Na_V1.1-1.9

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.

NaV1.3: Background Information

Na_V1.3 is abundantly expressed in neuronal tissues during embryonic and neonatal stages of development and is rare in adult tissues. After axonal transection, Na_V1.3 is upregulated in dorsal root ganglia (DRG) neurons adding to the evidence that upregulation of Na_V1.3 may play a role in rendering axotomized DRG neurons hyperexcitable, thus contributing to neuropathic pain. It is thought that the fast activation and inactivation kinetics of Na_V1.3, together with its rapid repriming kinetics and persistent current component, contributes to the development of spontaneous ectopic discharges and sustained rates of firing characteristics of injured sensory nerves. Na_V1.3 is TTX sensitive.

Gene:
SCN3A

Human Protein:
UniProt Q9NY46

Tissue:
Brain neurons, peripheral neurons, injured neurons, spinal cord, heart

Function/ Application:
Excitability of neurons, generation of action potentials

Pathology:
Familial autism, deafness, epilepsy, pain

Interaction:
Contactin, β1 subunit, β3 subunit, β8 subunit, calmodulin, LRP, C1D

Modulator:
Tetrodotoxin, AFT-II, Vinpocetine, Flecainide, Lidocaine

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

Particularities:
Na_V 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

Publications

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.

2010 - Propranolol blocks cardiac and neuronal voltage-gated sodium channels

Patchliner publication in Frontiers in Pharmacology (2010)

Authors:
Wang D.W., Mistry A.M., Kahlig K.M., Kearney J.A, Xiang J., George Jr. A.L.