Gilmour R F, Zipes D P
Am J Physiol. 1985 Oct;249(4 Pt 2):H735-40. doi: 10.1152/ajpheart.1985.249.4.H735.
The purpose of this study was to investigate possible mechanisms to explain the positive inotropic effects of acetylcholine in canine cardiac Purkinje fibers. Action potentials and tension were recorded from Purkinje fibers in vitro using microelectrodes and a force transducer. Acetylcholine (10(-9) to 10(-4) M) produced a dose-dependent increase in tension that was blocked by atropine but not by propranolol, phentolamine, hexamethonium, or verapamil. At 10(-5) and 10(-4) M, acetylcholine increased action potential duration at 50% of repolarization (APD50) but did not affect resting membrane potential, action potential amplitude, Vmax, or action potential duration at 90% of repolarization (APD90). Isoproterenol (10(-7) M) shortened APD50 and APD90 and increased developed tension. Subsequent addition of acetylcholine (10(-5) M) prolonged APD50 and APD90 and decreased tension. Increasing extracellular Ca2+ concentration [( Ca2+]o) from 2.0 to 3.0 mM increased tension and shortened APD50. Addition of acetylcholine (10(-5) M) increased tension further and prolonged APD50. In K+-depolarized fibers high concentrations of acetylcholine (10(-4) M) restored excitability, but lower concentrations (10(-6) M) suppressed slow responses induced by isoproterenol. Thus acetylcholine alone or with elevated [Ca2+]o increased APD50 and tension and facilitated the induction of slow responses, yet in the presence of isoproterenol acetylcholine increased APD50, decreased tension, and suppressed slow responses. These effects were mediated by muscarinic receptors and were independent of catecholamine release.
本研究的目的是探究可能的机制，以解释乙酰胆碱对犬心脏浦肯野纤维的正性肌力作用。使用微电极和力传感器在体外记录浦肯野纤维的动作电位和张力。乙酰胆碱（10⁻⁹至10⁻⁴M）使张力呈剂量依赖性增加，该作用被阿托品阻断，但不被普萘洛尔、酚妥拉明、六甲铵或维拉帕米阻断。在10⁻⁵和10⁻⁴M时，乙酰胆碱增加复极化50%时的动作电位时程（APD50），但不影响静息膜电位、动作电位幅度、Vmax或复极化90%时的动作电位时程（APD90）。异丙肾上腺素（10⁻⁷M）缩短APD50和APD90并增加张力。随后加入乙酰胆碱（10⁻⁵M）可延长APD50和APD90并降低张力。将细胞外Ca²⁺浓度[Ca²⁺]o从2.0 mM增加到3.0 mM可增加张力并缩短APD50。加入乙酰胆碱（10⁻⁵M）可进一步增加张力并延长APD50。在K⁺去极化的纤维中，高浓度的乙酰胆碱（10⁻⁴M）恢复兴奋性，但较低浓度（10⁻⁶M）抑制异丙肾上腺素诱导的慢反应。因此，单独的乙酰胆碱或与升高的[Ca²⁺]o一起可增加APD50和张力并促进慢反应的诱导，但在存在异丙肾上腺素的情况下，乙酰胆碱增加APD50，降低张力并抑制慢反应。这些作用由毒蕈碱受体介导，且与儿茶酚胺释放无关。
