Cytoplasmic [Ca2+] in mammalian ventricle: dynamic control by cellular processes.
A quantitative reconstruction of [Ca2+]i transients is the desired goal, but that goal has yet to be reached. It will be reached by solving Equation 2., once an adequate mathematical description of all its terms is obtained. If computed [Ca2+]i transients match closely those recorded under many experimental conditions, then we can be confident that our understanding of the cellular processes that control [Ca2+]i is correct. The SL Ca2+ ATPase and the SL Ca2+ leak do not make an important contribution on a given beat. All the available data, physiologic and biochemical, indicate clearly that the Ca2+ fluxes via the SL Ca2(+)-ATPase and SL Ca2(+)-leak pathways are small in comparison to others. Over many beats, however, the fluxes through these pathways will contribute to loading of the SR with Ca2+. In the abnormal case of resting cardiac muscle, [Ca2+]i will be determined by the balance between Ca2+ influx via leak and Ca2+ efflux via Na/Ca exchange and SL Ca2+ ATPase. There is an emerging consensus that the amount of Ca2+ entering via Na/Ca exchange during normal activity is small. This consensus derives from direct observation of changes in [Ca2+]i attributable to Na/Ca exchange, from computations that utilize new quantitative data on the current-voltage relation of the exchanger and on the quantitative relationship of exchanger current to [Ca2+]i. Clearly, the efflux of Ca2+ via Na/Ca exchange on each beat is significant. From theory and the fact that SL Ca2+ pumping is small, the efflux of Ca2+ via the exchanger must equal the Ca2+ influx through SL Ca2+ channels, but experimental studies have not yet verified this quantitatively. All the studies, recent and older, indicate that the [Ca2+]i transient in all mammalian species is dominated by Ca2+ released from SR. Even in the rat, widely believed to be the species most dependent on SR, the Ca2+ current contributes measurable Ca2+ (24). Provided that the SR is not depleted by rest, it is the major cellular entity that determines the [Ca2+]i transient in mammalian ventricular tissue on a given beat. Quantitative knowledge of the flux of Ca2+ from it, required for evaluating theories of excitation-contraction coupling, still awaits determination.
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
W G
WG
Wier
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism*; D004594:Electrophysiology; D006352:Heart Ventricles; D008322:Mammals / Q000378:metabolism*; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D002118:Calcium