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Published Online March 18, 2004
Science DOI: 10.1126/science.1094113

Research Articles

Submitted on December 1, 2003
Accepted on February 19, 2004

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*, Bernd Fakler 1*

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

* To whom correspondence should be addressed. E-mail: peter.jonas{at}physiologie.uni-freiburg.de, bernd.fakler{at}physiologie.uni-freiburg.de.

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 {beta} subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. Here 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.


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