The Journal of General Physiology
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Published online 17 July 2006 doi:10.1085/jgp.200609561
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 128, Number 2, 203-217
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ARTICLE

 A Trapped Intracellular Cation Modulates K+ Channel Recovery From Slow Inactivation



Evan C. Ray and Carol Deutsch

Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104

Correspondence to Carol Deutsch: cjd{at}mail.med.upenn.edu

Upon depolarization, many voltage-gated potassium channels undergo a time-dependent decrease in conductance known as inactivation. Both entry of channels into an inactivated state and recovery from this state govern cellular excitability. In this study, we show that recovery from slow inactivation is regulated by intracellular permeant cations. When inactivated channels are hyperpolarized, closure of the activation gate traps a cation between the activation and inactivation gates. The identity of the trapped cation determines the rate of recovery, and the ability of cations to promote recovery follows the rank order K+ > NH4+ > Rb+ > Cs+ >> Na+, TMA. The striking similarity between this rank order and that for single channel conductance suggests that these two processes share a common feature. We propose that the rate of recovery from slow inactivation is determined by the ability of entrapped cations to move into a binding site in the channel's selectivity filter, and refilling of this site is required for recovery.

Abbreviations used in this paper: FR, fractional recovery; I, inactivated; NI, noninactivated; TMA, tetramethylammonium.


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