Is ryanodine receptor a calcium or magnesium channel? Roles of K⁺ and Mg²⁺ during Ca²⁺ release

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• 作者：Dirk Gillespie ; ^{dirk_gillespie@rush.edu} ; Haiyan Chen ; Michael Fill
• 关键词：Ryanodine receptor ; Calcium release ; Magnesium ; Modeling
• 刊名：Cell Calcium
• 出版年：2012
• 期刊代码：7_01434160
• 类别：bio
• 出版时间：June, 2012
• 卷：51
• 期：6
• 页码：427-433
• 文件大小：640 K

摘要

The ryanodine receptor (RyR) is a poorly selective channel that mediates Ca²⁺ release from intracellular Ca²⁺ stores. How RyR's selectivity between the physiological cations K⁺, Mg²⁺, and Ca²⁺ affects single-channel Ca²⁺ current amplitude is examined using a recent model of RyR permeation. It is found that K⁺ provides the vast majority of the countercurrent (through RyR itself) that is needed to prevent the sarcoplasmic reticulum (SR) membrane potential from changing and stopping Ca²⁺ release. Moreover, intra-pore competition between Ca²⁺ and Mg²⁺ defines single RyR Ca²⁺ current amplitude. Since both [Mg²⁺] and [Ca²⁺]_SR can change during pathophysiological conditions, the RyR unitary Ca²⁺ current amplitude during Ca²⁺ release may change significantly due to this Ca²⁺/Mg²⁺ competition. Compared to the classic action of Mg²⁺ on RyR open probability, these Ca²⁺ current amplitude changes have as large or larger effects on overall RyR Ca²⁺ mobilization. A new aspect of RyR divalent versus monovalent selectivity is also identified where this kind of selectivity decreases as divalent concentration increases.