Changes in membrane currents in bullfrog atrium produced by acetylcholine.

Abstract

A double sucrose-gap voltage-clamp technique was used to study the effects of acetylcholine on the membrane currents in atrial trabeculae of the bullfrog, Rana catesbeiana. The 2nd, or slow inward (Ca2+/Na+) current, was markedly reduced by concentrations of acetylcholine greater than approximately 2.0 .times. 10-8 M. The resulting decrease in net Ca entry provided a straightforward explanation for the negative inotropic action of acetylcholine in atrial muscle. Measurements of membrane resistance near the resting potential showed that relatively high doses of acetylcholine (approximately 10-7 M) decreased membrane resistance by about 2-fold. This effect was the result of an increase in a time-independent background current which appears to be carried mainly by K+. Using appropriate pharmacological techniques the peak slow inward current was reduced to about half its initial value before any significant increase in background current occured. Even when a sufficient dose of acetylcholine to produce an increase in background current was used, the background current showed inward-going rectification and did not account for the observed reduction in the slow inward current. 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. 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.