Changes in membrane currents in bullfrog atrium produced by acetylcholine.

Abstract

SUMMARY1. A double sucrose-gap voltage-clamp technique has been used to study the effects of acetylcholine on the membrane currents in atrial trabeculae of the bullfrog, Rana catesbeiana.2. The second, or slow inward (Ca2+/Na+) current, was found to be markedly reduced by concentrations of acetylcholine greater than approximately 2-0 x 10-8 M. The resulting decrease in net calcium entry provides a straightforward explanation for the negative inotropic action of acetylcholine in atrial muscle.3. Measurements of membrane resistance near the resting potential showed that relatively high doses of acetylcholine (approximately 10-7 M) decrease membrane resistance by about twofold. This effect is shown to be the result of an increase in a time-independent background current which appears to be carried mainly by potassium ions.4. Using appropriate pharmacological techniques, it has been possible to demonstrate: (i) that the peak slow inward current is reduced to about half its initial value before any significant increase in background current occurs; (ii) that even when a sufficient dose of acetylcholine to produce an increase in background current is used, the background current shows inward-going rectification and cannot account for the observed reduction in the slow inward current.5. No consistent change was observed in the degree of activation of the time-dependent outward membrane currents after application of concentrations of acetylcholine which produced large decreases in the peak slow inward current.6. These results are discussed in relation to previous electro-physiological and radioisotope studies of the mechanism of the negative inotropic effect of acetylcholine in cardiac muscle.

The action of acetylcholine on background conductance in frog atrial trabeculae.

“…3C, D). The doseresponse curves give an estimate of the threshold concentration around 10-8 M. This result is not in agreement with Giles & Noble (1976) (Fig. 4).…”

“…6B. This curve has the characteristic shape of an inward rectifier and is very similar to the one given by Giles & Noble (1976). It must be noticed that the instantaneous or fully activated current-voltage relation of the I.,, current described by Noble & Tsien (1969) (Fig.…”

“…In fact, it has been shown by Ikemoto & Goto (1975), Giles & Noble (1976), Garnier et al (1976a that ACh behaves also as if it was an inhibitor of the slow inward current.…”

“…This effect was previously considered as a consequence of the shortening of the action potential duration resulting from an increase in K permeability (Burgen & Terrroux, 1953;Antoni & Rothmann, 1968). More recently Prokopezuk, Lewartowsky & Czarnecka (1973), Giles & Tsien (1975); Ikemoto & Goto (1975), Garnier, Goupil, Nargeot & Ojeda (1976a), Giles & Noble (1976) reported evidence that the negative inotropic effect could also be mediated by a decrease of the slow inward current. 382 D. GARNIER, J. NARGEOT, C. OJEDA AND 0.…”

Acetylcholine increases voltage-activated Ca2+ current in freshly dissociated smooth muscle cells.

“…We now describe an additional muscarinic action on these single smooth muscle cells-an increase in the magnitude and slowing of the decay of voltage-activated Ca2+ current. This excitatory action of acetylcholine stands in marked contrast to its inhibitory effect on cardiac muscle, where it suppresses voltage-activated Ca2+ current and activates an inwardly rectifying K+ current (13)(14)(15)(16). Brief accounts of this work have been reported in abstract form (17,18).…”