Contribution of the Na+/Ca2+ exchanger to rapid Ca2+ release in cardiomyocytes

Trigger Ca(2+) is considered to be the Ca(2+) current through the L-type Ca(2+) channel (LTCC) that causes release of Ca(2+) from the sarcoplasmic reticulum. However, cell contraction also occurs in the absence of the LTCC current (I(Ca)). In this article, we investigate the contribution of the Na(+...

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Bibliographic Details
Published in:Biophysical journal 2006-08, Vol.91 (3), p.779-792
Main Authors: Lines, Glenn T, Sande, Jørn B, Louch, William E, Mørk, Halvor K, Grøttum, Per, Sejersted, Ole M
Format: Article
Language:English
Subjects:
Animals
Biophysical Theory and Modeling
Biophysics - methods
Calcium - chemistry
Cells, Cultured
Diffusion
Male
Microscopy, Confocal
Models, Statistical
Models, Theoretical
Myocytes, Cardiac - metabolism
Rats
Rats, Wistar
Sarcoplasmic Reticulum - metabolism
Sodium-Calcium Exchanger - chemistry
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Summary:Trigger Ca(2+) is considered to be the Ca(2+) current through the L-type Ca(2+) channel (LTCC) that causes release of Ca(2+) from the sarcoplasmic reticulum. However, cell contraction also occurs in the absence of the LTCC current (I(Ca)). In this article, we investigate the contribution of the Na(+)/Ca(2+) exchanger (NCX) to the trigger Ca(2+). Experimental data from rat cardiomyocytes using confocal microscopy indicating that inhibition of reverse mode Na(+)/Ca(2+) exchange delays the Ca(2+) 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(2+) 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(2+) 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 four orders of magnitude lower than in water, triggering through LTCC alone was up to 5 ms slower than with the presence of a Na(+) channel and NCX.
ISSN:0006-3495
1542-0086
DOI:10.1529/biophysj.105.072447