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The Journal of Neuroscience, April 25, 2007, 27(17):4707-4715; doi:10.1523/JNEUROSCI.0758-07.2007

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Cellular/Molecular
BK Channels with ß3a Subunits Generate Use-Dependent Slow Afterhyperpolarizing Currents by an Inactivation-Coupled Mechanism

Xu-Hui Zeng, G. Richard Benzinger, Xiao-Ming Xia, and Christopher J. Lingle

Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110

Correspondence should be addressed to Christopher J. Lingle, Department of Anesthesiology, Washington University School of Medicine, Box 8054, St. Louis, MO 63110. Email: clingle{at}morpheus.wustl.edu

Large-conductance, Ca²⁺- and voltage-activated K⁺ (BK) channels are broadly expressed proteins that respond to both cellular depolarization and elevations in cytosolic Ca²⁺. The characteristic functional properties of BK channels among different cells are determined, in part, by tissue-specific expression of auxiliary ß subunits. One important functional property conferred on BK channels by ß subunits is inactivation. Yet, the physiological role of BK channel inactivation remains poorly understood. Here we report that as a consequence of a specific mechanism of inactivation, BK channels containing the ß3a auxiliary subunit exhibit an anomalous slowing of channel closing. This produces a net repolarizing current flux that markedly exceeds that expected if all open channels had simply closed. Because of the time dependence of inactivation, this behavior results in a Ca²⁺-independent but time-dependent increase in a slow tail current, providing an unexpected mechanism by which use-dependent changes in slow afterhyperpolarizations might regulate electrical firing. The physiological significance of inactivation in BK channels mediated by different ß subunits may therefore arise not from inactivation itself, but from the differences in the amplitude and duration of repolarizing currents arising from the ß-subunit-specific energetics of recovery from inactivation.

Key words: inactivation; BK channels; afterhyperpolarization; auxiliary subunits; excitability; gating

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Received Feb. 19, 2007; revised March 23, 2007; accepted March 23, 2007.

Correspondence should be addressed to Christopher J. Lingle, Department of Anesthesiology, Washington University School of Medicine, Box 8054, St. Louis, MO 63110. Email: clingle{at}morpheus.wustl.edu

This article has been cited by other articles:

				X. Zeng, X.-M. Xia, and C. J. Lingle Species-specific Differences among KCNMB3 BK {beta}3 Auxiliary Subunits: Some {beta}3 N-terminal Variants May Be Primate-specific Subunits J. Gen. Physiol., June 30, 2008; 132(1): 115 - 129. [Abstract] [Full Text] [PDF]

				N. Savalli, A. Kondratiev, S. B. de Quintana, L. Toro, and R. Olcese Modes of Operation of the BKCa Channel {beta}2 Subunit J. Gen. Physiol., July 1, 2007; 130(1): 117 - 131. [Abstract] [Full Text] [PDF]

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