Zucchi R, Ronca-Testoni S, Limbruno U, Yu G, Galbani P, Ronca G, Mariani M
Istituto di Cardiologia, University of Pisa, Italy.
J Cardiovasc Pharmacol. 1992;20 Suppl 7:S11-5.
We investigated the effect of gallopamil on cardiac sarcoplasmic reticulum (SR) function. Heavy SR was prepared from bovine ventricular muscle. Oxalate-supported calcium uptake was stimulated by gallopamil at concentrations ranging from 10 to 300 nM, whereas higher concentrations were ineffective. Peak stimulation averaged 25-30% of control calcium uptake and was observed at free calcium concentrations ranging from 1 to 6 microM. Calcium uptake is actually the difference between active calcium transport by SR calcium-adenosine triphosphate (calcium-ATPase), and passive efflux through SR calcium-release channels. In the presence of 300 microM of ryanodine, a blocker of SR channels, calcium uptake increased by 43% under control conditions, but not further stimulation was produced by gallopamil. SR calcium-ATPase was not affected by gallopamil. Similar results were obtained when oxalate-supported calcium uptake was determined with use of unfractionated homogenate obtained from rat hearts. We conclude that gallopamil acts on SR calcium-release channels and reduces the probability of channel opening and/or channel conductivity. The dose-response curve is bell shaped, and the maximum effect, which corresponds to 65% of the maximum effect of ryanodine, is achieved at therapeutic concentrations. Such action might contribute to the beneficial effect of gallopamil in the treatment of myocardial ischemia.
我们研究了加洛帕米对心肌肌浆网（SR）功能的影响。从牛心室肌制备重肌浆网。加洛帕米在10至300 nM的浓度范围内刺激草酸盐支持的钙摄取，而更高的浓度则无效。峰值刺激平均为对照钙摄取的25 - 30%，在1至6 microM的游离钙浓度下观察到。钙摄取实际上是肌浆网钙 - 三磷酸腺苷（钙 - ATP酶）的主动钙转运与通过肌浆网钙释放通道的被动外流之间的差异。在存在300 microM的兰尼碱（一种肌浆网通道阻滞剂）的情况下，在对照条件下钙摄取增加了43%，但加洛帕米未产生进一步刺激。肌浆网钙 - ATP酶不受加洛帕米影响。当使用从大鼠心脏获得的未分级匀浆测定草酸盐支持的钙摄取时，得到了类似的结果。我们得出结论，加洛帕米作用于肌浆网钙释放通道，降低通道开放的概率和/或通道传导性。剂量 - 反应曲线呈钟形，在治疗浓度下达到最大效应，该最大效应相当于兰尼碱最大效应的65%。这种作用可能有助于加洛帕米在治疗心肌缺血中的有益作用。
