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Am J Physiol Heart Circ Physiol 286: H971-H978, 2004. First published November 26, 2003; doi:10.1152/ajpheart.00308.2003
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Developmental changes of intracellular Ca2+ transients in beating rat hearts

Ariel L. Escobar,1 Roberta Ribeiro-Costa,1 Carlos Villalba-Galea,1 María Elena Zoghbi,1 Claudia G. Pérez,2 and Rafael Mejía-Alvarez2

1Department of Physiology, Health Sciences Center, Texas Tech University, Lubbock, Texas 79430; and 2Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinios 60153

Submitted 3 April 2003 ; accepted in final form 7 November 2003

Postnatal maturation of the rat heart is characterized by major changes in the mechanism of excitation-contraction (E-C) coupling. In the neonate, the t tubules and sarcoplasmic reticulum (SR) are not fully developed yet. Consequently, Ca2+-induced Ca2+ release (CICR) does not play a central role in E-C coupling. In the neonate, most of the Ca2+ that triggers contraction comes through the sarcolemma. In this work, we defined the contribution of the sarcolemmal Ca2+ entry and the Ca2+ released from the SR to the Ca2+ transient during the first 3 wk of postnatal development. To this end, intracellular Ca2+ transients were measured in whole hearts from neonate rats by using the pulsed local field fluorescence technique. To estimate the contribution of each Ca2+ flux to the global intracellular Ca2+ transient, different pharmacological agents were used. Ryanodine was applied to evaluate ryanodine receptor-mediated Ca2+ release from the SR, nifedipine for dihydropyridine-sensitive L-type Ca2+ current, Ni2+ for the current resulting from the reverse-mode Na+/Ca2+ exchange, and mibefradil for the T-type Ca2+ current. Our results showed that the relative contribution of each Ca2+ flux changes considerably during the first 3 wk of postnatal development. Early after birth (1–5 days), the sarcolemmal Ca2+ flux predominates, whereas at 3 wk of age, CICR from the SR is the most important. This transition may reflect the progressive development of the t tube-SR units characteristic of mature myocytes. We have hence directly defined in the whole beating heart the developmental changes of E-C coupling previously evaluated in single (acutely isolated or cultured) cells and multicellular preparations.

neonate; ryanodine receptor; cardiac excitation-contraction coupling; intact heart



Address for reprint requests and other correspondence: R. Mejía-Alvarez, Dept. of Physiology, Loyola Univ. Chicago, 2160 S. First Ave., Maywood, IL 60153 (E-mail: rmejia{at}lumc.edu).




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