A MOLECULAR-BASIS FOR GATING MODE TRANSITIONS IN HUMAN SKELETAL-MUSCLE NA+ CHANNELS

Recombinant sodium channel alpha subunits expressed in Xenopus oocytes display an anomalously slow rate of inactivation that arises from channels that predominantly exist in a slow gating mode [1,21. Co-expression of Na+ channel beta1 subunit with the human skeletal muscle Na+ channel alpha subunit increases the Na+ current and induces normal gating behavior in Xenopus laevis oocytes. The effects of the beta1 subunit can be explained by an allosterically induced conformational switch of the alpha subunit protein that occurs upon binding the beta1 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 beta1 subunit for gating mode changes of Na+ channels.