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

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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The biological and molecular properties of tetrodotoxin (TTX)-sensitive voltage-gated Na+ currents (INa) 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 Cd2+, and was abolished by TTX (K d = 11.2 nM), mibefradil (Kd=3.3 μM), 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 (Vhalf) inactivation and activation of INa 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 α-subunit protein of NaV1.6 were detected in smooth muscle layers. Using NaV1.6-null mice (NaV1.6 -/-) lacking the expression of the Na+ channel gene, Scn8a, INa were not detected in dispersed smooth muscle cells from the vas deferens, while TTX-sensitive INa were recorded in their wild-type (NaV1.6+/+) littermates. This study demonstrates that the molecular identity of the voltage-gated Na+ channels responsible for the TTX-sensitive INa in murine vas deferens myocytes is primarily NaV1.6.

Original languageEnglish
Pages (from-to)3340-3351
Number of pages12
JournalBiophysical Journal
Volume94
Issue number8
DOIs
Publication statusPublished - Apr 15 2008

All Science Journal Classification (ASJC) codes

  • Biophysics

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