EFFECTS OF COCAINE ON SARCOPLASMIC-RETICULUM IN SKINNED RAT-HEART MUSCLE

被引:10
作者
TOMITA, F
BASSETT, AL
MYERBURG, RJ
KIMURA, S
机构
[1] UNIV MIAMI,SCH MED,DEPT MED,DIV CARDIOL R94,MIAMI,FL 33101
[2] UNIV MIAMI,DEPT MOLEC & CELLULAR PHARMACOL,MIAMI,FL 33101
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 264卷 / 03期
关键词
CALCIUM SENSITIVITY; CALCIUM RELEASE AND UPTAKE;
D O I
10.1152/ajpheart.1993.264.3.H845
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 mug/ml for Ca2+ release and uptake studies and 200 mug/ml for Ca2+-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 muM cocaine and 5 mM caffeine increased caffeine-induced Ca2+ release by 15.7 +/- 3.1% (P < 0.05). However, when Ca2+-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 muM) had no effect on the Ca2+ sensitivity of the contractile system. We conclude that cocaine at a concentration of 50 muM 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.
引用
收藏
页码:H845 / H850
页数:6
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