Circulation Research, Vol 53, 740-751, Copyright © 1983 by American Heart Association

ARTICLES

Effects of acetylcholine on electrophysiological properties of rabbit cardiac Purkinje fibers

K Mubagwa and E Carmeliet

The action of acetylcholine (10(-9)-10(-4) M) was investigated in isolated rabbit cardiac Purkinje fibers, using standard microelectrode recording of transmembrane potentials and two-microelectrode voltage clamp technique. In nonstimulated fibers, acetylcholine hyperpolarized the diastolic membrane potential and slowed or suppressed spontaneous activity. The hyperpolarization was more pronounced in low potassium solutions and in depolarized fibers; it was less marked in the presence of cesium (2 X 10(-2) M), and was suppressed by barium (3-5 X 10(-3) M). In stimulated fibers, acetylcholine shortened the action potential duration and shifted the plateau level to more negative values; this effect was influenced little by the stimulation frequency and not by chloride removal from the perfusing solution. In voltage-clamped preparations, acetylcholine shifted the holding current in the outward direction at potentials less negative than EK, while it shifted the current in the inward direction at potentials more negative than EK. The changes induced by acetylcholine were concentration-dependent (apparent KM: 1.5 X 10(-7) M); they were mimicked by carbachol (10(-8)- 10(-5) M) and blocked by atropine (10(-8)-10(-7) M). The time course of the effects was biphasic: a maximum was reached in the first minute after addition of acetylcholine; thereafter, the effect decayed to a steady value. On removal of acetylcholine, a transient inversion of the changes produced by acetylcholine was observed, the magnitude of which depended on the acetylcholine concentration used and on the duration of exposure to acetylcholine. This time course was not abolished by pretreatment with physostigmine (10(-6) M), manganese ions (2 X 10(-3) M), or with adrenoceptor blockers [propranolol (2 X 10(-7) M) and/or phentolamine (10(-7)-10(-6) M)]. The results show that rabbit Purkinje fibers are as sensitive to acetylcholine as atrial preparations. The changes produced by acetylcholine are suggestive of an increase in an inward rectifying potassium ion conductance and are mediated by muscarinic receptor stimulation. The secondary decay in the effects of acetylcholine and their inversion on washout can be explained by a desensitization mechanism if it is assumed that the acetylcholine- sensitive channel is already functional in the absence of acetylcholine and is modulated in its conductance and/or open state probability by acetylcholine.

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