Phosphorylation of a K+ channel alpha subunit modulates the inactivation conferred by a beta subunit. Involvement of cytoskeleton.
Voltage-gated K+ channels isolated from mammalian brain are composed of alpha and beta subunits. Interaction between coexpressed Kv1.1 (alpha) and Kvbeta1.1 (beta) subunits confers rapid inactivation on the delayed rectifier-type current that is observed when alpha subunits are expressed alone. Integrating electrophysiological and biochemical analyses, we show that the inactivation of the alphabeta current is not complete even when alpha is saturated with beta, and the alphabeta current has an inherent sustained component, indistinguishable from a pure alpha current. We further show that basal and protein kinase A-induced phosphorylations at Ser-446 of the alpha protein increase the extent, but not the rate, of inactivation of the alphabeta channel, without affecting the association between alpha and beta. In addition, the extent of inactivation is increased by agents that lead to microfilament depolymerization. The effects of phosphorylation and of microfilament depolymerization are not additive. Taken together, we suggest that phosphorylation, via a mechanism that involves the interaction of the alphabeta channel with microfilaments, enhances the extent of inactivation of the channel. Furthermore, phosphorylation at Ser-446 also increases current amplitudes of the alphabeta channel as was shown before for the alpha channel. Thus, phosphorylation enhances in concert inactivation and current amplitudes, thereby leading to a substantial increase in A-type activity.
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, 69978 Ramat Aviv, Israel. ilotan@post.tav.ac.il
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Levin
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Chikvashvili
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Singer-Lahat
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Peretz
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Thornhill
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Lotan
D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism*; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012333:RNA, Messenger