Calcium sparks and [Ca2+]i waves in cardiac myocytes.
Local elevations in intracellular calcium ("Ca2+ sparks") in heart muscle are elementary sarcoplasmic reticulum (SR) Ca(2+)-release events. Ca2+ sparks occur at a low rate in quiescent cells but can also be evoked by electrical stimulation of the cell to produce the cell-wide Ca2+ transient. In this study we investigate how Ca2+ sparks are related to propagating waves of elevated cytosolic Ca2+ induced by "Ca2+ overload." Single ventricular myocytes from rat were loaded with the Ca(2+)-sensitive indicator fluo 3 and imaged with a confocal microscope. After extracellular Ca2+ concentration was increased from 1 to 10 mM to produce Ca2+ overload, the frequency of spontaneous Ca2+ sparks, which occur at the t tubule/SR junction, increased approximately 4-fold, whereas the spark amplitude and spatial size increased 4.1-and 1.7-fold, respectively. In addition, a spectrum of larger subcellular events, including propagating Ca2+ waves, was observed. Ca2+ sparks were seen to occur at the majority (65%) of the sites of wave initiation. For slowly propagating Ca2+ waves, discrete Ca(2+)-release events, similar to Ca2+ sparks, were detected in the wave front. These Ca2+ sparks appeared to recruit other sparks along the wave front so that the wave progressed in a saltatory manner. We conclude that Ca2+ sparks are elementary events that can explain both the initiation and propagation of Ca2+ waves. In addition, we show that Ca2+ waves and electrically evoked Ca2+ transients have the same time course and interact with each other in a manner that is consistent with both phenomena having the same underlying mechanism(s). These results suggest that SR Ca2+ release during Ca2+ waves, like that during normal excitation-contraction coupling, results from the spatial and temporal summation of Ca2+ sparks.
Cheng
H
H
Department of Physiology, University of Maryland, Baltimore School of Medicine 21201, USA.
Lederer
M R
MR
Lederer
W J
WJ
Cannell
M B
MB
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D007091:Image Processing, Computer-Assisted; D007425:Intracellular Membranes / Q000378:metabolism*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D002118:Calcium