BK channels with β3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism

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Abstract

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 β subunits. One important functional property conferred on BK channels by β 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 β3a 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 after hyperpolarizations might regulate electrical firing. The physiological significance of inactivation in BK channels mediated by different β subunits may therefore arise not from inactivation itself, but from the differences in the amplitude and duration of repolarizing currents arising from the β-subunit-specific energetics of recovery from inactivation.

Original languageEnglish
Pages (from-to)4707-4715
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number17
DOIs
StatePublished - Apr 25 2007

Keywords

  • Afterhyperpolarization
  • Auxiliary subunits
  • BK channels
  • Excitability
  • Gating
  • Inactivation

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