The action of muscarinic agonists and antagonists on frog atrial fibers. Electrophysiological studies.

Voltage clamp experiments have been conducted on frog atrial fibers to study the mechanism of the negative inotropic effect induced by muscarinic agonists. The results have shown that muscarinic agonists exert a dual effect: 1.) A reduction of the slow inward current (Is) amplitude; 2.) An increase in the potassium conductance. Dose-effect curves for both Is and K+ extra-current show that the inhibition of Is appears at lower agonist concentrations and can mainly account for the negative inotropic effect. It is suggested that the action of muscarinic agonists may involve one or two types of muscarinic receptors. The slow channel conductance could be controlled by the intracellular cyclic nucleotides concentration (cAMP and cGMP) via a muscarinic receptor (R1) with a high affinity for agonists. The increase in the potassium conductance could be mediated either by an increase in the intracellular free Ca2+ concentration or by a second type of muscarinic receptor (R2) with a lower affinity for muscarinic agonists and controlling a specific potassium channel.