A molecular basis for gating mode transitions in human skeletal muscle Na+ channels

FEBS Letters

George, Alfred L.¹  Bennett, Paul B.¹  Makita, Naomasa¹ 

[1] Departments of Pharmacology and Medicine, Vanderbilt University Medical School, Nashville, TN 37232-2171, USA

关键词: Na+ channel;    INa;    Inactivation;    Gating;    Subunit;   

DOI  :  10.1016/0014-5793(93)81752-L

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recombinant sodium channel α subunits expressed in Xenopus oocytes display an anomalously slow rate of inactivation that arises from channels that predominantly exist in a slow gating mode [1,2]. Co-expression of Na⁻ channel β₁ subunit with the human skeletal muscle Na⁺ channel α subunit increases the Na⁺ current and induces normal gating behavior in Xenopus laevis oocytes. The effects of the β₁ subunit can be explained by an allosterically induced conformational switch of the α subunit protein that occurs upon binding the β₁ subunit. This binding alters the free energy barriers separating distinct conformational states of the channel. The results illustrate a fundamental modulation of ion channel gating at the molecular level, and specifically demonstrate the importance of the β₁ subunit for gating mode changes of Na⁺ channels.

【 授权许可】

Unknown