Malécot C O, Arlock P, Katzung B G
J Pharmacol Exp Ther. 1985 Jan;232(1):10-9.
The effects of the cardiotonic agent, amrinone (0.05-4 mM), on electrical and mechanical activities of ferret and guinea-pig papillary muscles were studied using current and voltage clamp (single sucrose gap) techniques. In current clamp studies, amrinone increased, in a dose-dependent manner, contractile force elicited by action potential in both species. Depolarization-induced automaticity was facilitated in ferret muscles at all maximum diastolic potentials between -70 and -15 mV. Facilitation of automaticity in guinea-pig muscles occurred only at potentials more negative than -35 mV and was suppressed at more positive potentials. Cimetidine (10 microM) partially reversed the effects of amrinone on automaticity in both species. In voltage clamp studies, amrinone increased the slow inward current. Steady-state outward current was increased in guinea-pig but not in ferret muscles. A dual effect of amrinone on tension was observed. Amrinone was found to increase phasic tension of ferret papillary muscles only for depolarizations lasting less than 250 to 300 msec. For longer depolarizations, amrinone decreased the phasic tension (in a dose-dependent manner), whereas the tonic tension was not modified. The decrease as well as the increase in tension was associated with an increase of the slow inward current. The results suggest that amrinone may be arrhythmogenic and may have an intracellular action at the sarcoplasmic reticulum level (partial inhibition) in addition to its action on the calcium current.
使用电流钳和电压钳（单蔗糖间隙）技术研究了强心剂氨力农（0.05 - 4 mM）对雪貂和豚鼠乳头肌电活动和机械活动的影响。在电流钳研究中，氨力农以剂量依赖的方式增加了两种动物动作电位引发的收缩力。在雪貂肌肉中，在 -70 至 -15 mV 之间的所有最大舒张电位下，去极化诱导的自律性均增强。豚鼠肌肉中的自律性增强仅发生在电位比 -35 mV 更负时，而在更正的电位下受到抑制。西咪替丁（10 microM）部分逆转了氨力农对两种动物自律性的影响。在电压钳研究中，氨力农增加了慢内向电流。豚鼠肌肉中的稳态外向电流增加，而雪貂肌肉中未增加。观察到氨力农对张力有双重作用。仅在持续时间小于 250 至 300 毫秒的去极化情况下，氨力农才增加雪貂乳头肌的相位张力。对于更长时间的去极化，氨力农（以剂量依赖的方式）降低了相位张力，而强直张力未改变。张力的降低和增加均与慢内向电流的增加有关。结果表明，氨力农可能具有致心律失常作用，并且除了对钙电流的作用外，可能在肌浆网水平具有细胞内作用（部分抑制）。
