This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sánchez, G. Articles by Donoso, P. Search for Related Content PubMed PubMed Citation Articles by Sánchez, G. Articles by Donoso, P.

Kinetic Studies of Calcium-Induced Calcium Release in Cardiac Sarcoplasmic Reticulum Vesicles

Gina Sánchez^*, Cecilia Hidalgo^*, and Paulina Donoso^*

^*Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 70005, Santiago 7, Chile; and Centro de Estudios Científicos, Valdivia, Chile

Correspondence: Address reprint requests to Dr. Paulina Donoso, ICBM, Facultad de Medicina, Universidad de Chile, Casilla 70005, Santiago 7, Chile. Tel.: 56-2-678-6602; Fax: 56-2-777-6916; E-mail: pdonoso{at}machi.med.uchile.cl.

Fast Ca²⁺ release kinetics were measured in cardiac sarcoplasmic reticulum vesicles actively loaded with Ca²⁺. Release was induced in solutions containing 1.2 mM free ATP and variable free [Ca²⁺] and [Mg²⁺]. Release rate constants (k) were 10-fold higher at pCa 6 than at pCa 5 whereas Ryanodine binding was highest at pCa 5. These results suggest that channels respond differently when exposed to sudden [Ca²⁺] changes than when exposed to Ca²⁺ for longer periods. Vesicles with severalfold different luminal calcium contents exhibited double exponential release kinetics at pCa 6, suggesting that channels undergo time-dependent activity changes. Addition of Mg²⁺ produced a marked inhibition of release kinetics at pCa 6 (K_0.5 = 63 µM) but not at pCa 5. Coexistence of calcium activation and inhibition sites with equally fast binding kinetics is proposed to explain this behavior. Thimerosal activated release kinetics at pCa 5 at all [Mg²⁺] tested and increased at pCa 6 the K_0.5 for Mg²⁺ inhibition, from 63 µM to 136 µM. We discuss the possible relevance of these results, which suggest release through RyR2 channels is subject to fast regulation by Ca²⁺ and Mg²⁺ followed by time-dependent regulation, to the physiological mechanisms of cardiac channel opening and closing.

This article has been cited by other articles:

				G. Sanchez, M. Escobar, Z. Pedrozo, P. Macho, R. Domenech, S. Hartel, C. Hidalgo, and P. Donoso Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection Cardiovasc Res, January 15, 2008; 77(2): 380 - 386. [Abstract] [Full Text] [PDF]

				A. Zahradnikova, M. Dura, I. Gyorke, A. L. Escobar, I. Zahradnik, and S. Gyorke Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1059 - C1070. [Abstract] [Full Text] [PDF]

				P. Aracena, G. Sanchez, P. Donoso, S. L. Hamilton, and C. Hidalgo S-Glutathionylation Decreases Mg2+ Inhibition and S-Nitrosylation Enhances Ca2+ Activation of RyR1 Channels J. Biol. Chem., October 31, 2003; 278(44): 42927 - 42935. [Abstract] [Full Text] [PDF]