期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 286, 期 3, 页码 H971-H978出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00308.2003
关键词
neonate; ryanodine receptor; cardiac excitation-contraction coupling; intact heart
资金
- NHLBI NIH HHS [HL-62571-01] Funding Source: Medline
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.
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