A Charged Residue in S4 Regulates Coupling among the Activation Gate, Voltage, and Ca super(2+) Sensors in BK Channels
Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. One difficulty in studying sensor- gate coupling is to distinguish whether a structural perturbation alters the function of the sensor,...
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Published in | The Journal of neuroscience Vol. 34; no. 37; pp. 12280 - 12288 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
10.09.2014
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Online Access | Get full text |
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Summary: | Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. One difficulty in studying sensor- gate coupling is to distinguish whether a structural perturbation alters the function of the sensor, the gate, or their coupling. BK channels are activated by membrane voltage and intracellular Ca super(2+) via allosteric mechanisms with coupling among the activation gate and sensors quantitatively defined, providing an excellent model system for studying sensor-gate coupling. By studying BK channels expressed in Xenopus oocytes, here we show that mutation E219R in S4 alters channel function by two independent mechanisms: one is to change voltage sensor activation, shifting voltage dependence, and increase valence of gating charge movements; the other is to regulate coupling among the activation gate, voltage sensor, and Ca super(2+) binding via electrostatic interactions with E321/E324 located in the cytosolic side of S6 in a neighboring subunit, resulting in a shift of the voltage dependence of channel opening and increased Ca super(2+) sensitivity. These results suggest a structural arrangement of the inner pore of BK channels differing from that in other voltage gated channels. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 0270-6474 1529-2401 |
DOI: | 10.1523/JNEUROSCI.1174-14.2014 |