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 [1,2]. Co-expression of Na+ channel beta 1 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 beta 1 subunit can be explained by an allosterically induced conformational switch of the alpha subunit protein that occurs upon binding the beta 1 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 beta 1 subunit for gating mode changes of Na+ channels.
Bennett
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PB
Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-2171.
Makita
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N
George
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D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004553:Electric Conductivity; D005260:Female; D006801:Humans; D015640:Ion Channel Gating; D009132:Muscles / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
D011994:Recombinant Proteins; D015222:Sodium Channels; D012964:Sodium