Ryanodine receptor function in newborn rat heart

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 5; pp. H2527 - H2540
• Main Authors: Perez, Claudia G, Copello, Julio A, Li, Yanxia, Karko, Kimberly L, Gomez, Leticia, Ramos-Franco, Josefina, Fill, Michael, Escobar, Ariel L, Mejia-Alvarez, Rafael
• Format: Journal Article
• Language: English
• Published: United States 01.05.2005
• Subjects: Age Factors; Animals; Animals, Newborn; Calcium - metabolism; Calcium-Transporting ATPases - metabolism; Female; Heart - physiology; Ion Channel Gating - physiology; Ligands; Male; Models, Cardiovascular; Myocardial Contraction - physiology; Myocardium - metabolism; Rats; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel - metabolism; Sarcoplasmic Reticulum - metabolism; Sarcoplasmic Reticulum Calcium-Transporting ATPases
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00188.2004

1 Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois; 2 Departmento de Fisiología, Biofísica y Neurosciencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico; and 3 Department of Physiology, Texas Tech University, Lubbock, Texas Submitted 26 February 2004 ; accepted in final form 11 December 2004 The role of ryanodine receptor (RyR) in cardiac excitation-contraction (E-C) coupling in newborns (NB) is not completely understood. To determine whether RyR functional properties change during development, we evaluated cellular distribution and functionality of sarcoplasmic reticulum (SR) in NB rats. Sarcomeric arrangement of immunostained SR Ca 2+ -ATPase (SERCA2a) and the presence of sizeable caffeine-induced Ca 2+ transients demonstrated that functional SR exists in NB. E-C coupling properties were then defined in NB and compared with those in adult rats (AD). Ca 2+ transients in NB reflected predominantly sarcolemmal Ca 2+ entry, whereas the RyR-mediated component was 13%. Finally, the RyR density and functional properties at the single-channel level in NB were compared with those in AD. Ligand binding assays revealed that in NB, RyR density can be up to 36% of that found in AD, suggesting that some RyRs do not contribute to the Ca 2+ transient. To test the hypothesis that RyR functional properties change during development, we incorporated single RyRs into lipid bilayers. Our results show that permeation and gating kinetics of NB RyRs are identical to those of AD. Also, endogenous ligands had similar effects on NB and AD RyRs: sigmoidal Ca 2+ dependence, stronger Mg 2+ -induced inhibition at low cytoplasmic Ca 2+ concentrations, comparable ATP-activating potency, and caffeine sensitivity. These observations indicate that NB rat heart contains fully functional RyRs and that the smaller contribution of RyR-mediated Ca 2+ release to the intracellular Ca 2+ transient in NB is not due to different single RyR channel properties or to the absence of functional intracellular Ca 2+ stores. Ca 2+ release; sarcoplasmic reticulum; excitation-contraction coupling 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 )