Referenced in: none

Automatically associated channels: Nav1.7 , Slo1

Title: A new Nav1.7 mutation in an erythromelalgia patient.

Authors: Mark Estacion, Yang Yang, Sulayman D Dib-Hajj, Lynda Tyrrell, Zhimiao Lin, Yong Yang, Stephen G Waxman

Journal, date & volume: Biochem. Biophys. Res. Commun., 2013 Mar 1 , 432, 99-104

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23376079

Abstract
Gain-of-function missense mutations of SCN9A gene, which encodes voltage-gated sodium channel Nav1.7, alter channel's biophysical properties causing painful disorders which are refractory to pharmacotherapy in the vast majority of patients. Here we report a novel SCN9A mutation (ca.T3947C) in exon 20 in a 9 year old patient, not present in 200 ethnically-matched control alleles; the mutation substitutes the invariant valine 1316 residue within DIII/S5 by alanine (V1316A). Voltage-clamp studies show that Nav1.7 V1316A mutation hyperpolarizes activation (-9 mV), and enhances response to ramp stimuli (3-fold), changes that are predicted to cause hyperexcitability of DRG neurons. V1316A also hyperpolarizes steady-state slow-inactivation (-9.9 mV), which is predicted to attenuate the effect of this mutation on DRG neuron firing. These changes are consistent with previously characterized Erytheromelalgia associated mutations of Nav1.7.