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Cell Calcium. 2012 Jun;51(6):427-33. doi: 10.1016/j.ceca.2012.02.001. Epub 2012 Mar 3.

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

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Department of Molecular Biophysics and Physiology, Section of Cellular Signaling, Rush University Medical Center, Chicago, IL 60612, United States.


The ryanodine receptor (RyR) is a poorly selective channel that mediates Ca(2+) release from intracellular Ca(2+) stores. How RyR's selectivity between the physiological cations K(+), Mg(2+), and Ca(2+) affects single-channel Ca(2+) 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 Ca(2+) release. Moreover, intra-pore competition between Ca(2+) and Mg(2+) defines single RyR Ca(2+) current amplitude. Since both [Mg(2+)] and [Ca(2+)](SR) can change during pathophysiological conditions, the RyR unitary Ca(2+) current amplitude during Ca(2+) release may change significantly due to this Ca(2+)/Mg(2+) competition. Compared to the classic action of Mg(2+) on RyR open probability, these Ca(2+) current amplitude changes have as large or larger effects on overall RyR Ca(2+) mobilization. A new aspect of RyR divalent versus monovalent selectivity is also identified where this kind of selectivity decreases as divalent concentration increases.

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