Differences in the regulation of RyR2 from human, sheep, and rat by Ca²⁺ and Mg²⁺ in the cytoplasm and in the lumen of the sarcoplasmic reticulum

Autor: Kafa, Walweel, Jiao, Li, Peter, Molenaar, Mohammad S, Imtiaz, Anthony, Quail, Cris G, dos Remedios, Nicole A, Beard, Angela F, Dulhunty, Dirk F, van Helden, Derek R, Laver
Rok vydání: 2014
Předmět:
Zdroj: The Journal of General Physiology
ISSN: 1540-7748
Popis: Cardiac ryanodine receptors (RyR2) from humans, rats, and sheep show differential sensitivity to calcium and magnesium, with regulation of human RyR2 resembling that of sheep more than that of rat.
Regulation of the cardiac ryanodine receptor (RyR2) by intracellular Ca2+ and Mg2+ plays a key role in determining cardiac contraction and rhythmicity, but their role in regulating the human RyR2 remains poorly defined. The Ca2+- and Mg2+-dependent regulation of human RyR2 was recorded in artificial lipid bilayers in the presence of 2 mM ATP and compared with that in two commonly used animal models for RyR2 function (rat and sheep). Human RyR2 displayed cytoplasmic Ca2+ activation (Ka = 4 µM) and inhibition by cytoplasmic Mg2+ (Ki = 10 µM at 100 nM Ca2+) that was similar to RyR2 from rat and sheep obtained under the same experimental conditions. However, in the presence of 0.1 mM Ca2+, RyR2s from human were 3.5-fold less sensitive to cytoplasmic Mg2+ inhibition than those from sheep and rat. The Ka values for luminal Ca2+ activation were similar in the three species (35 µM for human, 12 µM for sheep, and 10 µM for rat). From the relationship between open probability and luminal [Ca2+], the peak open probability for the human RyR2 was approximately the same as that for sheep, and both were ∼10-fold greater than that for rat RyR2. Human RyR2 also showed the same sensitivity to luminal Mg2+ as that from sheep, whereas rat RyR2 was 10-fold more sensitive. In all species, modulation of RyR2 gating by luminal Ca2+ and Mg2+ only occurred when cytoplasmic [Ca2+] was
Databáze: OpenAIRE
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