AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol (December 30, 2004). doi:10.1152/ajpheart.00188.2004
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Submitted on February 26, 2004
Accepted on December 11, 2004

Ryanodine receptor function in newborn rat heart

Claudia G. Perez1, Julio A. Copello1, Yanxia Li1, Kimberly L. Karko1, Leticia N. Gomez2, Josefina Ramos-Franco1, Michael Fill1, Ariel L. Escobar3, and Rafael Mejia-Alvarez1*

1 Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
2 Departmento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del I.P.N., Mexico, DF, Mexico; Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
3 Department of Physiology, Texas Tech University, Lubbock, TX, USA

* To whom correspondence should be addressed. E-mail: rmejia{at}lumc.edu.

The role of the ryanodine receptor (RyR) in cardiac excitation-contraction (E-C) coupling in newborn (NB) is not completely understood. Our goal was to determine whether the RyR functional properties change during development. To this end, the cellular distribution and functionality of the SR were evaluated in NB. Sarcomeric arrangement of immunostained Ca2+-ATPase (SERCA2a) and the presence of sizeable caffeine-induced Ca2+ transients demonstrated that functional SR exists in NB. E-C coupling properties were then defined in NB and compared to adult (AD). Ca2+ transients in NB reflected predominantly sarcolemmal Ca2+ entry, while the RyR-mediated component was ~13%. Finally, the NB RyR density and functional properties at the single-channel level were compared to AD. Ligand binding assays revealed that in NB RyRs density can be up to 36% of that found in AD. This suggested that some RyRs do not contribute to the Ca2+ transient. To test the hypothesis that the RyR functional properties change during development, single RyR were incorporated into lipid bilayers. Our results showed that permeation and gating kinetics of NB RyRs are identical to AD. Also, endogenous ligands had similar effects on NB and AD RyR: sigmoidal Ca2+ dependence, stronger Mg2+-induced inhibition at low cytoplasmic [Ca2+]'s, comparable ATP activating potency, and caffeine sensitivity. These observations indicated that NB rat heart contains fully functional RyRs and that the smaller contribution of RyR-mediated Ca2+ release to the intracellular Ca2+ transient in NB is not due to different single RyR channel properties, or to the absence of functional intracellular Ca2+ stores.




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