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

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.