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Molecular mechanisms of BK channel activation.

ABSTRACT: Large conductance, Ca(2+)-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability of BK channels to be synergistically activated by membrane voltage, intracellular Ca(2+) and other ligands. Similar to voltage-gated K(+) channels, BK channels possess a pore-gate domain (S5-S6 transmembrane segments) and a voltage-sensor domain (S1-S4). In addition, BK channels contain a large cytoplasmic C-terminal domain that serves as the primary ligand sensor. The voltage sensor and the ligand sensor allosterically control K(+) flux through the pore-gate domain in response to various stimuli, thereby linking cellular metabolism and membrane excitability. This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca(2+)- and Mg(2+)-dependent activation of the channel.

SUBMITTER: Cui J

PROVIDER: S-EPMC2694844 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Molecular mechanisms of BK channel activation.

Cui J J Yang H H Lee U S US

Cellular and molecular life sciences : CMLS 20090301 5

Large conductance, Ca(2+)-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability of BK channels to be synergistically activated by membrane voltage, intracellular Ca(2+) and other ligands. Similar to voltage-gated K(+) channels, BK channels possess a pore-gate domain (S5-S6 transmembrane segments) an ...[more]

PMID: 19099186

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Project description:BACKGROUND: BK channels are usually activated by membrane depolarization and cytoplasmic Ca(2+). Especially,the activity of BK channel (?+?4) can be modulated by martentoxin, a 37 residues peptide, with Ca(2+)-dependent manner. gBK channel (glioma BK channel) and BK channel (?+?1) possessed higher Ca(2+) sensitivity than other known BK channel subtypes. METHODOLOGY AND PRINCIPAL FINDINGS: The present study investigated the modulatory characteristics of martentoxin on these two BK channel subtypes by electrophysiological recordings, cell proliferation and Ca(2+) imaging. In the presence of cytoplasmic Ca(2+), martentoxin could enhance the activities of both gBK and BK channel (?+?1) subtypes in dose-dependent manner with EC(50) of 46.7 nM and 495 nM respectively, while not shift the steady-state activation of these channels. The enhancement ratio of martentoxin on gBK and BK channel (?+?1) was unrelated to the quantitative change of cytoplasmic Ca(2+) concentrations though the interaction between martentoxin and BK channel (?+?1) was accelerated under higher cytoplasmic Ca(2+). The selective BK pore blocker iberiotoxin could fully abolish the enhancement of these two BK subtypes induced by martentoxin, suggesting that the auxiliary ? subunit might contribute to the docking for martentoxin. However, in the absence of cytoplasmic Ca(2+), the activity of gBK channel would be surprisingly inhibited by martentoxin while BK channel (?+?1) couldn't be affected by the toxin. CONCLUSIONS AND SIGNIFICANCE: Thus, the results shown here provide the novel evidence that martentoxin could increase the two Ca(2+)-hypersensitive BK channel subtypes activities in a new manner and indicate that ? subunit of these BK channels plays a vital role in this enhancement by martentoxin.

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