Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/195324
Type: Artigo
Title: Contribution of Ca(2+) transporters to relaxation in intact ventricular myocytes from developing rats
Author: Rosana A. Bassani
JoséW. M. Bassani
Abstract: The relative contributions of Ca(2+) transporters to intracellular Ca(2+) concentration ([Ca(2+)](i)) decline associated with twitch relaxation were analyzed in intact ventricular myocytes from developing and adult rats. This was accomplished by estimation of individual integrated Ca(2+) fluxes with the use of kinetic parameters calculated from [Ca(2+)](i) measurements during twitches and caffeine-evoked contractures, and from myocardial passive Ca(2+) buffering data. Our main findings were the following: 1) twitch relaxation and [Ca(2+)](i) decline were significantly slower during the first postnatal week than in adults, 2) inhibition of sarcoplasmic reticulum (SR) Ca(2+) accumulation resulted in faster [Ca(2+)](i) decline in young cells than in adult cells, 3) the contributions of the SR Ca(2+) uptake and Na(+)/Ca(2+) exchange (NCX) to twitch relaxation increased from ~75 to 92%, and decreased from 24 to 5%, respectively, from birth to adulthood, and 4) Ca(2+) transport by the sarcolemmal Ca(2+)-ATPase was apparently increased in neonates. Our data indicate that despite a marked increase in NCX contribution to cell relaxation in immature rats, the SR Ca(2+)-ATPase appears to be the predominant transporter responsible for relaxation-associated [Ca(2+)](i) decline from birth to adulthood.
The relativ contributions of Ca2+ transporters to intracellular Ca2+ concentration ([Ca2+]i) decline associated with twitch relaxation were analyzed in intact ventricular myocytes from developing and adult rats. This was accomplished by estimation of individual integrated Ca2+fluxes with the use of kinetic parameters calculated from [Ca2+]i measurements during twitches and caffeine-evoked contractures, and from myocardial passive Ca2+ buffering data. Our main findings were the following:1) twitch relaxation and [Ca2+]idecline were significantly slower during the first postnatal week than in adults, 2) inhibition of sarcoplasmic reticulum (SR) Ca2+ accumulation resulted in faster [Ca2+]i decline in young cells than in adult cells, 3) the contributions of the SR Ca2+uptake and Na+/Ca2+ exchange (NCX) to twitch relaxation increased from ∼75 to 92%, and decreased from 24 to 5%, respectively, from birth to adulthood, and 4) Ca2+ transport by the sarcolemmal Ca2+-ATPase was apparently increased in neonates. Our data indicate that despite a marked increase in NCX contribution to cell relaxation in immature rats, the SR Ca2+-ATPase appears to be the predominant transporter responsible for relaxation-associated [Ca2+]i decline from birth to adulthood, considerable structural and functional changes take place in the mammalian ventricle after birth. The cell proliferation rate drops drastically while cells undergo marked differentiation and growth. In the rat, myocardial protein content is more than duplicated, the relative cell volume occupied by certain organelles [i.e., myofilaments, sarcoplasmic reticulum (SR), and mitochondria] is greatly increased, and the cell surface-to-volume ratio decreases at least two times within the first 2 postnatal weeks (10, 21, 28, 35,36). Development of the t-tubular system during this period (29) allows action potential conduction along more internal regions of the cell, thus compensating for increase in cell volume and permitting synchronous excitation of the cell as a whole. In the rat heart, expression of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2; both mRNA and protein levels), as well as Ca2+ uptake rates by SR vesicles, are reported to be low just after birth and to increase during postnatal development (17, 22, 35). In contrast, the Na+/Ca2+ exchanger (NCX) appears to undergo opposite developmental changes. Both mRNA and protein levels were found to be much higher in the neonatal heart than in the adult rat heart, with subsequent downregulation as maturation proceeds (11,35). Accordingly, the rate of Na+-dependent Ca2+ uptake by cardiac sarcolemmal vesicles from neonatal and young rats is considerably higher than in adults (35). Because SR Ca2+ uptake and Ca2+ extrusion via the NCX are the main pathways for [Ca2+]idecrease during relaxation of the adult mammalian ventricle (3,6, 27), it would be expected that these changes in SR Ca2+-ATPase (SR-ATPase) and NCX expression might result in major change in the individual contribution of each transporter to relaxation. That is, NCX, which is responsible for <10% of the Ca2+ transport during relaxation of adult rat myocytes (3, 27), would play a more prominent role in relaxation and might even equal or surpass the contribution of the SR Ca2+ uptake. Although marked ontogenetic changes in the relative roles of SR-ATPase and NCX in twitch relaxation might be expected from the available data on cell protein content and Ca2+ transport in subcellular preparations, it is difficult to predict the impact of these changes in the live cardiac cell. The importance of specific Ca2+transporters to relaxation-associated Ca2+ decline during postnatal development has been examined in only a few studies (2), and quantitative estimation of the relative contribution on these transporters is still lacking. Moreover, possible ontogenetic changes in transporters other than SR-ATPase and NCX have not been addressed so far. The purpose of the present study was to investigate the following:1) whether the relative participation of SR-ATPase and NCX in twitch relaxation of intact, isolated rat ventricular myocytes is actually altered during postnatal development, 2) the extent at which the contribution of each transporter is modified,3) the time course of these changes, and 4) possible developmental variation in the contribution of the mitochondrial Ca2+ uptake via the Ca2+uniporter (Mito-U) and sarcolemmal Ca2+-ATPase (SL-ATPase) to twitch relaxation. Our results indicate increased activity of SL-ATPase in preweaning rats (especially neonates), and much higher role of NCX in relaxation during the first postnatal week, compared with adults. However, the SR-ATPase is still the main transporter responsible for twitch relaxation, even in the neonatal rat ventricle
Subject: Transporte biologico
Reticulo sarcoplasmático
Country: Estados Unidos
Editor: American Physiological Society
Citation: American Journal Of Physiology. Heart And Circulatory Physiology. v. 282, n. 6, p. H2406-13, 2002-Jun.
Rights: fechado
fechado
Identifier DOI: 10.1152/ajpheart.00320.2001
Address: https://www.physiology.org/doi/full/10.1152/ajpheart.00320.2001
Date Issue: 2002
Appears in Collections:FEEC - Artigos e Outros Documentos
CEB - Artigos e Outros Documentos

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