Changes in membrane currents in bullfrog atrium produced by acetylcholine.

Abstract

1. 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. © 1976 The Physiological Society