title: Is ryanodine receptor a calcium or magnesium channel? Roles of K+ and Mg2+ during Ca2+ release.
abstract: 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.
authors.affiliation: Department of Molecular Biophysics and Physiology, Section of Cellular Signaling, Rush University Medical Center, Chicago, IL 60612, United States. dirk_gillespie@rush.edu
authors.forename: Dirk
authors.initials: D
authors.lastname: Gillespie
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Fill
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry*; D015220:Calcium Channels / Q000737:chemistry*; D002413:Cations, Divalent / Q000737:chemistry; D002414:Cations, Monovalent / Q000737:chemistry; D002463:Cell Membrane Permeability; D008274:Magnesium / Q000737:chemistry*; D008564:Membrane Potentials; D009132:Muscles / Q000737:chemistry; D011188:Potassium / Q000737:chemistry*; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry*; D012519:Sarcoplasmic Reticulum / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D015220:Calcium Channels; D002413:Cations, Divalent; D002414:Cations, Monovalent; D019837:Ryanodine Receptor Calcium Release Channel; D008274:Magnesium; D011188:Potassium; D002118:Calcium