Referenced in: none

Automatically associated channels: Nav1.6

Title: Molecular and biophysical properties of voltage-gated Na+ channels in murine vas deferens.

Authors: Hai-Lei Zhu, Manami Aishima, Hidetaka Morinaga, Richard D Wassall, Atsushi Shibata, Kazuomi Iwasa, Masatoshi Nomura, Masaya Nagao, Katsuo Sueishi, Thomas C Cunnane, Noriyoshi Teramoto

Journal, date & volume: Biophys. J., 2008 Apr 15 , 94, 3340-51

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18192366

Abstract
The biological and molecular properties of tetrodotoxin (TTX)-sensitive voltage-gated Na(+) currents (I(Na)) in murine vas deferens myocytes were investigated using patch-clamp techniques and molecular biological analyses. In whole-cell configuration, a fast, transient inward current was evoked in the presence of Cd(2+), and was abolished by TTX (K(d) = 11.2 nM), mibefradil (K(d) = 3.3 microM), and external replacement of Na(+) with monovalent cations (TEA(+), Tris(+), and NMDG(+)). The fast transient inward current was enhanced by veratridine, an activator of voltage-gated Na(+) channels, suggesting that the fast transient inward current was a TTX-sensitive I(Na). The values for half-maximal (V(half)) inactivation and activation of I(Na) were -46.3 mV and -26.0 mV, respectively. RT-PCR analysis revealed the expression of Scn1a, 2a, and 8a transcripts. The Scn8a transcript and the alpha-subunit protein of Na(V)1.6 were detected in smooth muscle layers. Using Na(V)1.6-null mice (Na(V)1.6(-/-)) lacking the expression of the Na(+) channel gene, Scn8a, I(Na) were not detected in dispersed smooth muscle cells from the vas deferens, while TTX-sensitive I(Na) were recorded in their wild-type (Na(V)1.6(+/+)) littermates. This study demonstrates that the molecular identity of the voltage-gated Na(+) channels responsible for the TTX-sensitive I(Na) in murine vas deferens myocytes is primarily Na(V)1.6.