Temma K, Akera T, Ng Y C
J Cardiovasc Pharmacol. 1985 Mar-Apr;7(2):297-306. doi: 10.1097/00005344-198503000-00015.
The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. In partially depolarized atrial muscle preparations, which were reactivated by elevation of the extracellular Ca2+ level and stimulation at a high voltage, phencyclidine markedly increased the amplitude and the duration of the slow action potentials. Rat heart muscle preparations had higher sensitivity to these effects of phencyclidine. The specific [3H]phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K+ currents.
在豚鼠和大鼠心脏的离体标本中研究了苯环利定正性肌力作用的机制。在电起搏的左心房肌标本中，苯环利定增强了收缩力；大鼠心肌标本比豚鼠心肌标本更敏感。酚妥拉明和纳多洛尔联合使用时，苯环利定的正性肌力作用没有显著降低；然而，在酚妥拉明和纳多洛尔存在的情况下，维拉帕米竞争性地阻断了该作用。氯化四乙铵抑制外向钾电流也产生了正性肌力作用；然而，四乙铵的作用被酚妥拉明和纳多洛尔减弱，并且对维拉帕米几乎不敏感。苯环利定的正性肌力作用与动作电位持续时间的显著延长以及动作电位最大上升速度的降低有关，静息膜电位无变化。在部分去极化的心房肌标本中，通过提高细胞外钙离子水平和高压刺激使其重新激活，苯环利定显著增加了慢动作电位的幅度和持续时间。大鼠心肌标本对苯环利定的这些作用更敏感。用豚鼠心室肌膜标本观察到的特异性[3H]苯环利定结合具有单一类高亲和力结合位点的饱和性。这种结合被维拉帕米、地尔硫卓或尼群地平抑制，但不被兰尼碱或河豚毒素抑制。这些结果表明，苯环利定的正性肌力作用是由于通过慢通道增强了钙离子内流，这要么是通过刺激通道，要么是继发于外向钾电流的抑制。
