可卡因对雪貂心室肌细胞内钙离子处理及肌丝钙离子反应性的影响。

The effects of cocaine on intracellular Ca2+ handling and myofilament Ca2+ responsiveness of ferret ventricular myocardium.

作者信息

Perreault C L, Hague N L, Ransil B J, Morgan J P

机构信息

Charles A. Dana Research Institute, Boston, MA.

出版信息

Br J Pharmacol. 1990 Nov;101(3):679-85. doi: 10.1111/j.1476-5381.1990.tb14140.x.

DOI:10.1111/j.1476-5381.1990.tb14140.x

PMID:2076484

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917724/

Abstract

When ferret right ventricular papillary muscles were stimulated with threshold punctate pulses (0.33 Hz; 30 degrees C), cocaine, 10(-5) M, increased peak tension development from 815 +/- 120 to 1125 +/- 180 mg (P less than 0.05) and increased the rate of relaxation from peak tension (time to 80% decline from peak tension decreased from 155 +/- 11 to 144 +/- 11 ms; P less than 0.05). These changes in the twitch were associated with comparable changes in the amplitude and time course of the calcium transient measured with aequorin (amplitude increased from 62 +/- 4 to 90 +/- 7% (P less than 0.05) of maximal values; time to 80% decline from peak amplitude decreased from 84 +/- 8 to 64 +/- 3 ms; P less than 0.05). These effects were markedly attenuated in the presence of the beta-adrenoceptor-blocking agent, propranolol, 6 x 10(-7) M, or by maximization of catecholamine release from the adrenergic nerve endings with field pulses of suprathreshold strength, indicating that catecholamine release from the adrenergic nerve endings is responsible for the positive inotropic and lusitropic responses to low and moderate doses of cocaine (i.e., less than or equal to 10(-5) M). 2. High doses of cocaine (i.e., greater than 10(-5) M) produced negative inotropic and lusitropic effects that were associated with a decreased amplitude and prolonged duration of the calcium transient. 3. In aequorin-loaded intact fibres, cocaine 10(-5) M did not affect the force-calcium relationship unless catecholamines were present. Cocaine, 10(-5) M, significantly shifted the force-calcium relationship of saponin-skinned muscles (pCa50 = 6.14 +/- 0.05 versus 5.92 +/- 0.07; P less than 0.05), indicating reduced responsiveness of the myofilaments to calcium. F. (maximal Ca2+-activated force) was reduced to 58% of control in the presence of 10- M cocaine, while the slope of the calcium-force curve remained unchanged. These data indicate that cocaine may also decrease myofilament calcium sensitivity and maximal calciumactivated force, via mechanisms independent of catecholamines, when cellular diffusion barriers are eliminated.

摘要

当用阈点状脉冲（0.33Hz；30℃）刺激雪貂右心室乳头肌时，10⁻⁵M的可卡因可使峰值张力从815±120mg增加至1125±180mg（P＜0.05），并使从峰值张力开始的舒张速率加快（从峰值张力下降80%的时间从155±11ms降至144±11ms；P＜0.05）。这些收缩变化与用水母发光蛋白测量的钙瞬变的幅度和时程的相应变化相关（幅度从最大值的62±4%增加至90±7%（P＜0.05）；从峰值幅度下降80%的时间从84±8ms降至64±3ms；P＜0.05）。在存在6×10⁻⁷M的β-肾上腺素能受体阻断剂普萘洛尔时，或通过用阈上强度的场脉冲使肾上腺素能神经末梢的儿茶酚胺释放最大化时，这些效应明显减弱，表明肾上腺素能神经末梢释放的儿茶酚胺是对低剂量和中等剂量可卡因（即≤10⁻⁵M）产生正性肌力和变时性反应的原因。2. 高剂量可卡因（即＞10⁻⁵M）产生负性肌力和变时性效应，这与钙瞬变幅度减小和持续时间延长有关。3. 在装载水母发光蛋白的完整纤维中，10⁻⁵M的可卡因在不存在儿茶酚胺时不影响力-钙关系。10⁻⁵M的可卡因使皂角苷透膜处理的肌肉的力-钙关系显著改变（pCa50 = 6.14±0.05对比5.92±0.07；P＜0.05），表明肌丝对钙的反应性降低。在存在10⁻⁵M可卡因时，F（最大Ca²⁺激活力）降至对照的58%，而钙-力曲线的斜率保持不变。这些数据表明，当细胞扩散屏障消除时，可卡因还可能通过与儿茶酚胺无关的机制降低肌丝钙敏感性和最大钙激活力。