Delbono O, Obejero Paz C A, Muchnik S
Laboratorio de Neurofisiología, Instituto de Investigaciones Médicas Alfredo Lanari, Buenos Aires, Argentina.
Acta Physiol Pharmacol Latinoam. 1987;37(4):423-35.
The effects of verapamil (0.01-0.1 mM) and Ca-free solutions (0 Ca, 3 mM MgCl2, 5 mM EGTA) upon mechanical and electrical properties of a fast twitch mammalian skeletal muscle (extensor digitorum longus) have been studied. Ca-free saline reduces twitch and tetanus tension. The response to single pulses was not affected in the presence of verapamil, but as the rate of stimulation increased, peak tensions were lower and a gradual decrease of tension was observed: frequency-dependent effect. Caffeine (30 mM) contracture was significantly reduced by both solutions. The fibers in Ca-free saline were depolarized (6 mV) and +dV/dt, -dV/dt and overshoot of the AP's were reduced. On the other hand, verapamil did not affect Vm. The presence of 0.1 mM verapamil hindered the ability of the fibers to generate AP's at high rates of stimulation. Lower concentration of verapamil (0.01) did not affect the repetitive electrical activity, but tetanic tension was decreased. These findings support partially the hypothesis about the dependence of mammalian skeletal muscle from external Ca. Verapamil would have several mechanisms of action: a) Ca-channel blocker action, b) local anaesthetic effect, and c) reduction of Ca release from the sarcoplasmic reticulum.
研究了维拉帕米(0.01 - 0.1 mM)和无钙溶液(0 Ca,3 mM MgCl2,5 mM EGTA)对快速收缩的哺乳动物骨骼肌(趾长伸肌)机械和电特性的影响。无钙生理盐水可降低单收缩和强直收缩张力。在维拉帕米存在的情况下,对单个脉冲的反应不受影响,但随着刺激频率增加,峰值张力降低,且观察到张力逐渐下降:频率依赖性效应。两种溶液均显著降低了咖啡因(30 mM)诱导的挛缩。无钙生理盐水中的纤维发生去极化(6 mV),动作电位的 +dV/dt、-dV/dt 和超射降低。另一方面,维拉帕米不影响膜电位(Vm)。0.1 mM 维拉帕米的存在阻碍了纤维在高刺激频率下产生动作电位的能力。较低浓度的维拉帕米(0.01)不影响重复电活动,但强直收缩张力降低。这些发现部分支持了关于哺乳动物骨骼肌对细胞外钙依赖性的假说。维拉帕米可能有几种作用机制:a)钙通道阻滞剂作用,b)局部麻醉作用,以及 c)减少肌浆网释放钙。