Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition

Abstract — Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca2+ and the perforated patch-clamp technique to measure SR Ca2+ content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca2+ (sparks and waves of Ca2+-induced Ca2+ release), increased SR Ca2+ content (79.4±5.7 to 115.2±6.6 &mgr;mol/L cell volume [mean±SEM;P <0.001]), and, after a wave of Ca2+ release, slower reuptake of Ca2+ into the SR (rate constant of fall of Ca2+ reduced from 8.5±1.1 s−1 in control to 5.2±0.4 s−1 in metabolic inhibition [P <0.01]). Inhibition of L-type Ca2+ channels with Cd2+ (100 &mgr;mol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca2+ sparks. These results are evidence of inhibition of both Ca2+ release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca2+ content at the time of reduced frequency of spontaneous release of Ca2+ shows that the dominant effect of metabolic inhibition is to inhibit release of Ca2+ from the SR, allowing the accumulation of greater than normal amounts of Ca2+. In the context of ischemia, this extra accumulation of Ca2+ would present a risk of potentially arrhythmogenic, spontaneous release of Ca2+ on reperfusion of the tissue.