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

Abstract

SUMMARY1. The ionic mechanisms underlying the effects of acetylcholine (ACh) on electrophysiological properties of rabbit cardiac Purkinje fibres have been analysed using the two-micro-electrode voltage-clamp technique on short preparations.2. In normal Tyrode solution, ACh shifted the membrane currents in the outward direction at potentials positive to the K+ equilibrium potential, EK, and in the inward direction at potentials negative to EK. When ACh effects were studied in various [K+].the reversal potential for the ACh-induced current was changed in a way expected for a pure K+ electrode. The results indicate an increase of an inward-rectifying K+ conductance by ACh.3. ACh also decreased the magnitude of the late outward current (ix). The activation curve for this current was not modified, but the fully activated current was decreased. The effect of ACh on ix was more pronounced in the presence of catecholamines.4. The slow inward current (isi) was not changed by ACh in control conditions. However, the increase produced by f-adrenergic stimulation in this current was suppressed by ACh in a concentration-dependent way.

Characterization of the acetylcholine‐induced potassium current in rabbit cardiac Purkinje fibres.

“…increased by ACh). In Carmeliet & Mubagwa (1986a), it was shown that ACh does not change the slow inward current in the absence of catecholamines. It is therefore unlikely that a steady component of the slow inward current accounts for the Cs+-insensitive ACh-induced component.…”

“…Changes in time-dependent currents might also contribute to the effect of ACh. A decrease of the late outward current, ix (see Carmeliet & Mubagwa, 1986a), would tend to superimpose on the effect of ACh on other currents. This will result in a total ACh-induced current decreasing with time during depolarizations to potentials positive to -50 mV and in an inward tail on return to the holding potential.…”

“…After having shown that ACh increases a K+ conductance (Carmeliet & Mubagwa, 1986a), it was interesting to investigate the characteristics of the ACh-sensitive K+ current. An important question to answer was whether the properties of this conductance are superimposable on those of the pre-existing inward rectifier iK1 (Garnier et al 1978;Ojeda et al 1981 ;Argibay et al 1983), or whether the ACh-sensitive current presents characteristics which suggest that it is different from iK1 (Noma & Trautwein, 1978;Sakmann et al 1983).…”

“…The experiments were carried out on isolated cardiac Purkinje fibres and the two-micro-electrode voltage-clamp technique used in the present experiments is the same as the one used previously (Carmeliet & Ramon, 1980; see also Carmeliet & Mubagwa, 1986a). …”

Desensitization of the acetylcholine‐induced increase of potassium conductance in rabbit cardiac Purkinje fibres.

“…In preparations pre-treated with catecholamines, ACh becomes able to decrease the amplitude of the slow inward current, isi (see Carmeliet & Mubagwa, 1986a), probably by antagonizing the stimulation produced by catecholamines on the adenylate cyclase system (Watanabe 243 E. CARMELIET AND K. MUBAGWA & Besch, 1975;Biegon & Pappano, 1980). The time course of the inhibitory effect of ACh on isj was investigated.…”