Mechanism of calcium gating in small-conductance calcium-activated potassium channels

X. M. Xia, B. Fakler, A. Rivard, G. Wayman, T. Johnson-Pais, J. E. Keen, T. Ishii, B. Hirschberg, C. T. Bond, S. Lutsenko, James Maylie, John Adelman

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Abstract

The slow afterhyperpolarization that follows an action potential is generated by the activation of small-conductance calcium-activated potassium channels (SK channels). The slow afterhyperpolarization limits the firing frequency of repetitive action potentials (spike-frequency adaption) and is essential for normal neurotransmission. SK channels are voltage-independent and activated by submicromolar concentrations of intracellular calcium. They are high-affinity calcium sensors that transduce fluctuations in intracellular calcium concentrations into changes in membrane potential. Here we study the mechanism of calcium gating and find that SK channels are not gated by calcium binding directly to the channel α-subunits. Instead, the functional SK channels are heteromeric complexes with calmodulin, which is constitutively associated with the α-subunits in a calcium-independent manner. Our data support a model in which calcium gating of SK channels is mediated by binding of calcium to calmodulin and subsequent conformational alterations in the channel protein.

Original languageEnglish (US)
Pages (from-to)503-507
Number of pages5
JournalNature
Volume395
Issue number6701
DOIs
StatePublished - Oct 1 1998

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Small-Conductance Calcium-Activated Potassium Channels
Calcium
Calmodulin
Action Potentials
Synaptic Transmission
Membrane Potentials

ASJC Scopus subject areas

  • General

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Xia, X. M., Fakler, B., Rivard, A., Wayman, G., Johnson-Pais, T., Keen, J. E., ... Adelman, J. (1998). Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature, 395(6701), 503-507. https://doi.org/10.1038/26758

Mechanism of calcium gating in small-conductance calcium-activated potassium channels. / Xia, X. M.; Fakler, B.; Rivard, A.; Wayman, G.; Johnson-Pais, T.; Keen, J. E.; Ishii, T.; Hirschberg, B.; Bond, C. T.; Lutsenko, S.; Maylie, James; Adelman, John.

In: Nature, Vol. 395, No. 6701, 01.10.1998, p. 503-507.

Research output: Contribution to journalArticle

Xia, XM, Fakler, B, Rivard, A, Wayman, G, Johnson-Pais, T, Keen, JE, Ishii, T, Hirschberg, B, Bond, CT, Lutsenko, S, Maylie, J & Adelman, J 1998, 'Mechanism of calcium gating in small-conductance calcium-activated potassium channels', Nature, vol. 395, no. 6701, pp. 503-507. https://doi.org/10.1038/26758
Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE et al. Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature. 1998 Oct 1;395(6701):503-507. https://doi.org/10.1038/26758
Xia, X. M. ; Fakler, B. ; Rivard, A. ; Wayman, G. ; Johnson-Pais, T. ; Keen, J. E. ; Ishii, T. ; Hirschberg, B. ; Bond, C. T. ; Lutsenko, S. ; Maylie, James ; Adelman, John. / Mechanism of calcium gating in small-conductance calcium-activated potassium channels. In: Nature. 1998 ; Vol. 395, No. 6701. pp. 503-507.
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