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Small conductance Ca 2+ ‐activated K + channels and calmodulin
Author(s) -
Maylie James,
Bond Chris T.,
Herson Paco S.,
Lee WeiSheng,
Adelman John P.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.049072
Subject(s) - sk channel , gating , apamin , biophysics , calcium activated potassium channel , conductance , chemistry , calmodulin , ion channel , potassium channel , afterhyperpolarization , electrophysiology , membrane potential , biochemistry , biology , neuroscience , physics , receptor , condensed matter physics , enzyme
Small conductance Ca 2+ ‐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 Ca 2+ 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 Ca 2+ gating in SK channels is due to heteromeric assembly of the SK α pore‐forming subunits with calmodulin (CaM). Ca 2+ 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, Ca 2+ ‐independent interactions between the SK channel α subunits and CaM are necessary for proper membrane trafficking.