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; J. Maylie; J. P. Adelman

doi:10.1038/26758

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, J. Maylie, J. P. Adelman

Obstetrics and Gynecology

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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 language	English (US)
Pages (from-to)	503-507
Number of pages	5
Journal	Nature
Volume	395
Issue number	6701
DOIs	https://doi.org/10.1038/26758
State	Published - Oct 1 1998

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title = "Mechanism of calcium gating in small-conductance calcium-activated potassium channels",

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.",

author = "Xia, {X. M.} and B. Fakler and A. Rivard and G. Wayman and T. Johnson-Pais and Keen, {J. E.} and T. Ishii and B. Hirschberg and Bond, {C. T.} and S. Lutsenko and J. Maylie and Adelman, {J. P.}",

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T1 - Mechanism of calcium gating in small-conductance calcium-activated potassium channels

AU - Xia, X. M.

AU - Fakler, B.

AU - Rivard, A.

AU - Wayman, G.

AU - Johnson-Pais, T.

AU - Keen, J. E.

AU - Ishii, T.

AU - Hirschberg, B.

AU - Bond, C. T.

AU - Lutsenko, S.

AU - Maylie, J.

AU - Adelman, J. P.

PY - 1998/10/1

Y1 - 1998/10/1

N2 - 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.

AB - 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.

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

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