Effects of cocaine on sarcoplasmic reticulum in skinned rat heart muscle

We examined the effects of cocaine on the ability of the sarcoplasmic reticulum (SR) to release and accumulate Ca2+ and on the Ca2+ sensitivity of the contractile proteins using chemically skinned rat left ventricular muscles. The preparations were treated with saponin (40 micrograms/ml for Ca2+ release and uptake studies and 200 micrograms/ml for Ca(2+)-tension experiments). The SR was loaded with 10(-6) M Ca2+ solution; SR Ca2+ release was induced by application of 5 or 25 mM caffeine. The amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. After 1 min of SR Ca2+ loading, simultaneous application of 50 microM cocaine and 5 mM caffeine increased caffeine-induced Ca2+ release by 15.7 +/- 3.1% (P < 0.05). However, when Ca(2+)-loaded preparations were treated with cocaine for 1 min before application of 5 mM caffeine, caffeine-induced Ca2+ release was reduced by 17.1 +/- 3.0% (P < 0.05). When cocaine was applied during the Ca2+ loading periods, the amount of Ca2+ accumulated by the SR (the area under the 25 mM caffeine-induced contraction) increased for both 1-min (10.9 +/- 1.7%, P < 0.05) and 3-min (15.5 +/- 4.4%, P < 0.05) Ca2+ loading periods. Cocaine (50 microM) had no effect on the Ca2+ sensitivity of the contractile system. We conclude that cocaine at a concentration of 50 microM can directly alter the ability of the SR to release and accumulate Ca2+. These effects of cocaine, especially those on SR Ca2+ release, may play a role in its potential for induction of cardiac toxicity.