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Science 304 (5668): 265-270

Copyright © 2004 by the American Association for the Advancement of Science

Functional Conversion Between A-Type and Delayed Rectifier K+ Channels by Membrane Lipids

Dominik Oliver,1* Cheng-Chang Lien,1* Malle Soom,2 Thomas Baukrowitz,2 Peter Jonas,1{dagger} Bernd Fakler1{dagger}

Abstract: Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct {alpha} and ß subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.

1 Institute of Physiology, University of Freiburg, Hermann-Herder-Straße 7, 79104 Freiburg, Germany.
2 Institute of Physiology II, University of Jena, Teichgraben 8, 07744 Jena, Germany.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: bernd.fakler{at}physiologie.uni-freiburg.de (B.F.) and peter.jonas{at}physiologie.uni-freiburg.de (P.J.)


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