Small conductance Ca2+-activated K+ channels and calmodulin

James Maylie, Chris T. Bond, Paco S. Herson, Wei Sheng Lee, John Adelman

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Small conductance Ca2+-activated K+ channels (SK channels) contribute to the long lasting afterhyperpolarization (AHP) that follows an action potential in many central neurones. The biophysical and pharmacological attributes of cloned SK channels strongly suggest that one or more of them underlie the medium component of the AHP that regulates interspike interval and plays an important role in setting tonic firing frequency. The cloned SK channels comprise a distinct subfamily of K+ channels. Heterologously expressed SK channels recapitulate the biophysical and pharmacological hallmarks of native SK channels, being gated solely by intracellular Ca2+ ions with no voltage dependence to their gating, small unitary conductance values and sensitivity to the bee venom peptide toxin, apamin. Molecular, biochemical and electrophysiological studies have revealed that Ca2+ gating in SK channels is due to heteromeric assembly of the SK α pore-forming subunits with calmodulin (CaM). Ca2+ binding to the N-terminal E-F hands of CaM is responsible for SK channel gating. Crystallographic studies suggest that SK channels gate as a dimer-of-dimers, and that the physical gate of SK channels resides at or near the selectivity filter of the channels. In addition, Ca2+-independent interactions between the SK channel α subunits and CaM are necessary for proper membrane trafficking.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalJournal of Physiology
Volume554
Issue number2
DOIs
StatePublished - Jan 15 2004

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Calcium-Activated Potassium Channels
Calmodulin
Pharmacology
Bee Venoms
Apamin
Action Potentials
Hand
Ions
Neurons

ASJC Scopus subject areas

  • Physiology

Cite this

Small conductance Ca2+-activated K+ channels and calmodulin. / Maylie, James; Bond, Chris T.; Herson, Paco S.; Lee, Wei Sheng; Adelman, John.

In: Journal of Physiology, Vol. 554, No. 2, 15.01.2004, p. 255-261.

Research output: Contribution to journalArticle

Maylie, James ; Bond, Chris T. ; Herson, Paco S. ; Lee, Wei Sheng ; Adelman, John. / Small conductance Ca2+-activated K+ channels and calmodulin. In: Journal of Physiology. 2004 ; Vol. 554, No. 2. pp. 255-261.
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