AuthorsG. T. Lines, J. B. Sande, W. E. Louch, H. K. Mørk, P. Grøttum and O. M. Sejersted
TitleContribution of the Na/Ca Exchanger to Rapid Ca Release in Cardiomyocytes
AfilliationScientific Computing, Scientific Computing
StatusPublished
Publication TypeJournal Article
Year of Publication2006
JournalBiophysical Journal
Volume91
Number3
Pagination779-792
Abstract

Trigger Ca is considered to be the Ca current through the L-type Ca channel (LTCC) that causes release of Ca from the sarcoplasmic reticulum (SR). However, cell contraction also occurs in the absence of the LTCC current (ICa). In this paper we investigate the contribution of the Na/Ca -exchanger (NCX) to the trigger Ca. Experimental data from rat cardiomyocytes using confocal microscopy indicating that inhibition of reverse mode Na/Ca -exchange delays the Ca transient by 3-4 ms, served as a basis for the mathematical model. A detailed computational model of the dyadic cleft (fuzzy space) is presented where the diffusion of both Na and Ca is taken into account. Ionic channels are included at discrete locations, making it possible to study the effect of channel position and colocalization. The simulations indicate that if a Na channel is present in the fuzzy space, the NCX is able to bring enough Ca into the cell to affect the timing of release. However, this critically depends on channel placement and local diffusion properties. With fuzzy space diffusion in the order of 1% compared to bulk diffusion, triggering through LTCC alone was 3-4 ms slower than with the presence of a Na channel and NCX.

Citation KeyLines.2006.1