Cytosolic calcium transients from the beating mammalian heart.

To elucidate the role of cytosolic calcium, Ca2+i, in the physiology of the normal and ischemic heart, we have developed a method for recording Ca2+i transients from the epicardial surface of the rabbit ventricle after arterial perfusion with the cell-permeant cytosolic calcium indicator indo-1 AM. Hearts were illuminated at 360 nm, and fluorescence was recorded simultaneously at 400 and 550 nm. The F400/F550 fluorescence ratio was calculated by an analog circuit that allowed cancelation of small movement artifacts that were present at single wavelengths. Clear Ca2+i transients were present in the F400/F550 signal and were remarkable for their slow decay. Slow decay of the transients was not due to buffering of Ca2+i by indo-1, since there was no associated impairment of contraction or relaxation. The peak amplitude of the Ca2+i transients was increased by ouabain, adrenaline, postextrasystolic potentiation, and acetylcholine. The extent to which the transients decayed diminished with shortening of the interbeat interval, but decay of the transients could be further diminished by acetylcholine or caffeine. A major advantage of the intact heart over isolated myocytes is the ability to measure changes in Ca2+i during ischemia. Ischemia produced a marked increase in both peak systolic and end-diastolic Ca2+i, which was most rapid during the first 30 sec, and approached a plateau value after 90 sec. This increase in Ca2+i was associated with a characteristic broadening of the peak of the transient. The increase in Ca2+i during ischemia is consistent with a proposed causative role of Ca2+i in mediating early electrophysiological abnormalities.