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Distribution of excitation-contraction coupling proteins as a function of development

University of British Columbia

Excitation-contraction (EC) coupling in the neonatal rabbit heart has been previously shown to be mediated predominately by reverse-mode activity of the sodium-calcium exchanger (NCX). Thus the regulation of NCX is a primary determinant of neonatal cardiac contractility. It is proposed that in neonate hearts, a restricted domain allows a sodium current (INa) to mediate a large elevation in subsarcolemmal sodium concentration which then drives calcium entry through reverse-mode NCX. Functional data suggest that calcium influx through NCX can also trigger calcium induced calcium release (CICR). Traditionally, neonatal myocytes are thought to mediate EC coupling exclusively through trans-sarcolemma calcium influx. This model of EC coupling is distinct from the adult model of EC coupling in that it does not involve a significant CICR component. Traditionally, CICR processes are thought to be a hallmark of adult EC coupling processes where CICR is triggered exclusively by the L-type calcium current. Neonatal myocytes were previously believed to be too immature to sustain physiologically significant levels of CICR. Yet recent functional data suggest that not only are neonatal myocytes able to sustain CICR but that neonatal myocytes trigger CICR independently of the calcium current. Neonatal myocytes appear to trigger CICR exclusively though reverse-mode NCX activity (NCX-CICR). The phenomenon of NCX-CICR, prominent in early developmental stages and declining with further development, suggest that the neonatal myocardium contains specialized microdomains that allow NCX-CICR to occur. To investigate this unique EC coupling phenotype, three-dimensional confocal microscopy and advanced digital image analysis techniques are utilized to quantify the presence of these specialized microdomains and to determine the changes in these microdomains that occur with development.

Text

2010-02-19

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/20563

Physiology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/