Temma K, Akera T, Brody T M, Rech R H
J Pharmacol Exp Ther. 1983 Sep;226(3):885-92.
Chronotropic and inotropic actions of phencyclidine were studied in spontaneously beating right atrial muscle and electrically paced left atrial muscle preparations isolated from guinea-pig or rat hearts. In right atrial muscle preparations, phencyclidine (10-100 microM) decreased the frequency of spontaneous beating. Guinea-pig and rat heart preparations had similar sensitivities to this action of phencyclidine. The negative chronotropic effect was not altered by atropine. A high concentration of naloxone failed to affect the chronotropic effect of phencyclidine in guinea-pig muscle, but significantly reduced the effect in rat heart muscle preparations. Phencyclidine (1-100 microM) caused positive inotropic effects in both guinea-pig and rat heart left atrial muscle electrically stimulated at 1.5 Hz; rat heart preparations had a higher sensitivity to the positive inotropic action of phencyclidine. The positive inotropic effect was reduced by verapamil, nifedipine and relatively high concentrations of diltiazem, but was not affected by propranolol, phentolamine, tripelennamine, atropine or ryanodine, indicating that the effect is not mediated by adrenergic, histaminergic or cholinergic systems or does not involve ryanodine-sensitive calcium pools. Inactivation of the fast sodium channels by partial membrane depolarization, and subsequent restoration of the contraction by raising the extracellular Ca++ concentration, did not abolish the positive inotropic action of phencyclidine. These results suggest that the negative chronotropic effect of phencyclidine is not mediated by a stimulation of the muscarinic receptor. The positive inotropic effects of phencyclidine seem to result from an increase in Ca++ influx through the slow channels of the cardiac cell membrane.
在从豚鼠或大鼠心脏分离出的自发搏动右心房肌和电刺激左心房肌标本中，研究了苯环利定的变时性和变力性作用。在右心房肌标本中，苯环利定（10 - 100微摩尔）降低了自发搏动频率。豚鼠和大鼠心脏标本对苯环利定的这一作用具有相似的敏感性。负性变时作用不受阿托品影响。高浓度纳洛酮未能影响苯环利定对豚鼠心肌的变时作用，但显著降低了其对大鼠心肌标本的作用。苯环利定（1 - 100微摩尔）在1.5赫兹电刺激的豚鼠和大鼠心脏左心房肌中均产生正性变力作用；大鼠心脏标本对苯环利定的正性变力作用更敏感。维拉帕米、硝苯地平和相对高浓度的地尔硫卓可降低正性变力作用，但普萘洛尔、酚妥拉明、曲吡那敏、阿托品或ryanodine对其无影响，表明该作用不是由肾上腺素能、组胺能或胆碱能系统介导，也不涉及ryanodine敏感的钙池。部分膜去极化使快速钠通道失活，随后通过提高细胞外Ca++浓度恢复收缩，并未消除苯环利定的正性变力作用。这些结果表明，苯环利定的负性变时作用不是由毒蕈碱受体刺激介导的。苯环利定的正性变力作用似乎是由于通过心肌细胞膜慢通道的Ca++内流增加所致。
