H. Satoh et al., EFFECTS OF [CA2+](I), SR CA2+ LOAD, AND REST ON CA2+ SPARK FREQUENCY IN VENTRICULAR MYOCYTES, American journal of physiology. Heart and circulatory physiology, 41(2), 1997, pp. 657-668
In heart, spontaneous local increases in cytosolic Ca2+ concentration
([Ca2+](i)) called ''Ca2+ sparks'' may be fundamental events underlyin
g both excitation-contraction coupling and resting Ca2+ leak from the
sarcoplasmic reticulum (SR). In this study, resting Ca2+ sparks were a
nalyzed in rabbit and rat ventricular myocytes with laser scanning con
focal microscopy and the fluorescent Ca2+ indicator flue 3. During the
first 20 s of rest after regular electrical stimulation, both the fre
quency of Ca2+ sparks and SR Ca2+ content gradually decreased in rabbi
t. When rabbit SR Ca2+ content was decreased by reduction of stimulati
on rate, the initial resting spark frequency was also decreased, even
though resting [Ca2+](i) was unchanged. The rest-dependent decrease in
spark frequency in rabbit cells was prevented by inhibition of Na+/Ca
2+ exchange (which also prevents SR Ca2+ depletion during rest). These
results suggest that elevation of SR Ca2+ content can increase Ca2+ s
park frequency. In contrast to rabbit cells, 20 s of rest produced a g
radual increase in spark frequency in rat cells, although SR Ca2+ cont
ent was constant and Ca2+ influx was completely prevented. This indica
tes that there is a time-dependent increase in spark probability durin
g rest that is independent of [Ca2+](i) or SR Ca2+. This effect was al
so apparent in rabbit cells when SR Ca2+ depletion was prevented by bl
ocking Na+/Ca2+ exchange. Stimulation of Ca2+ extrusion via Na+/Ca2+ e
xchange in the rat (by Ca2+-free superfusion, which slowly depletes SR
Ca2+ content) converted the normal rest-dependent increase in spark f
requency to a decrease. The amplitude of individual Ca2+ sparks increa
sed with increasing SR Ca2+ content. In the Ca2+-overloaded state, fus
ion of sparks or long-lasting localized increases of [Ca2+](i) were ob
served with increased spark frequency. We conclude that the resting fr
equency of Ca2+ sparks can be independently affected by changes in SR
Ca2+ content, [Ca2+](i), or rest period. The latter may reflect recove
ry of the SR Ca2+ release channels from inactivation or adaptation.