Effect of acetylcholine on membrane currents in guinea‐pig papillary muscle.

Abstract

SUMMARY1. The effect of acetylcholine (ACh) on the membrane current components in guinea-pig papillary muscle was studied by the single sucrose gap voltage clamp method.2. The slow inward current (i.) elicited by various depolarizations from the holding potential of -40 mV was evidently diminished by ACh greater than 5 x 10-7 M. The amplitude of i5, estimated as the difference between the peak of i.and the current at 150 msec, was reduced to 56-8 + 12-9 % (mean + S.D., n = 34) by 2 x 10-6 M-ACh when estimated at the membrane potential where the amplitude was maximal.3. is was suppressed almost completely by 2 mM-Co2+. i8 obtained by subtracting the current remaining in 2 mMCo2+ was also diminished to the same extent by 2 x 10-6 M-ACh with little change in its time course; the degree of decrease was not dependent on the membrane potential.4. The time-dependent outward current during the depolarizing pulse was also diminished by 2 x 10-6 M-ACh. Correspondingly, the positive tail current obtained when the membrane was repolarized to the holding potential of -40 mV after various 1 see depolarizations was reduced in a proportionate manner to 68-6 + 7-3 %

Changes by acetylcholine of membrane currents in rabbit cardiac Purkinje fibres.

“…8), contrary to what is observed in frog atrial preparations (Giles & Noble, 1976) and in guinea-pig papillary muscle (Hino & Ochi, 1980). isi was decreased by ACh only after it had been increased by pre-treatment with catecholamines.…”

“…Since it has been shown that ACh may also decrease the slow inward current in many preparations (Giles & Noble, 1976;Ten Eick et al 1976;Ikemoto & Goto, 1977;Hino & Ochi, 1980), we also investigated this possible mechanism in rabbit cardiac Purkinje fibres. The effects of ACh on i were studied in the absence and in the presence of adrenergic stimulation.…”

The effects of vagal stimulation and applied acetylcholine on the sinus venosus of the toad.

“…The other two effects result in changes in inward current flow through separate voltage-dependent channels. Acetylcholine suppresses slow inward current (isi, Brown, 1982) through voltage-dependent calcium channels of both amphibian (Giles & Tsien, 1975;Ikemoto & Goto, 1975; Giles & Noble, 1976) and mammalian cardiac muscle (Ten Eick, Nawath, McDonald & Trautwein, 1976;Hino & Ochi, 1980). In the studies on non-pacemaker tissues, lower concentrations of acetylcholine were required to reduce isi than to activate the potassium current.…”

Antimuscarinic action of quinidine on the heart? A study in myocardial preparations from cat hearts

“…The reversal by promazine of acetylcholine-induced changes in rat atrial action potentials (Landmark, Haffner & Lindberg, 1973) and the antagonistic effects of 4-aminopyridine (Freeman, 1979) were interpreted in the same way. The potassium system in ventricular heart muscle is obviously not affected by acetylcholine (Ochi & Hino, 1976;Hino & Ochi, 1980). This may explain why the effects of acetylcholine are inhibited by quinidine in atrial but not in ventricular heart muscle.…”

“…TenEick et al (1976) concluded that the enhancement of the potassium conductance is of major importance since the calcium-dependent slow inward current was only inhibited at very high concentrations of acetylcholine. Recently, Ochi & Hino (1978) and Hino & Ochi (1980) described the effects of acetylcholine in guinea-pig ventricular myocardium. These authors found that acetylcholine decreased the calcium-dependent slow inward current without any effect on the potassium conductance.…”