High-conductance calcium-activated potassium channels; Structure,pharmacology, and function |
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Authors: | Gregory J. Kaczorowski Hans -Günther Knaus Reid J. Leonard Owen B. McManus Maria L. Garcia |
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Affiliation: | (1) Merck Research Laboratories, P.O. Box 2000, 07065 Rahway, New Jersey;(2) Institute for Biochemical Pharmacology, University of Innsbruck, Peter-Mayr Strasse 1, A-6020 Innsbruck, Austria |
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Abstract: | High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, and . The subunit is a member of theslo Ca2+-activated K+ channel gene family and forms the ion conduction pore. The subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against and subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets. |
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Keywords: | maxi-K channels charybdotoxin iberiotoxin smooth muscle ion channel purification slo channels /content/g58030125853nt03/xxlarge914.gif" alt=" Bgr" align=" BASELINE" BORDER=" 0" >-subunit K channel agonists K channel blockers ion channel pharmacology |
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