On the time course of the acetylcholine-induced hyperpolarization in quiescent guinea-pig atria

The time course of the action of acetylcholine (ACh) released from postganglionic parasympathetic nerve endings was studied in quiescent preparations of right atria from the guinea-pig heart. ACh release was induced by stimulation with single impulses subthreshold for excitation of atrial muscle cells. After stimulation a hyperpolarization of the atrial cell membrane could be recorded. At 35 degrees C time to peak (ttp) was reached 580--890 ms after the stimulus pulse. The hyperpolarization declined exponentially with a time constant of 1.6--3.4 s. The early rising phase was proportional to t3 where t is time and displayed a Q10 of about 12. The decay was less temperature-dependent (Q10 of ca. 1.5). Superfusion with solutions containing caffeine (0.25--2.0 mM) an inhibitor of cyclic nucleotide phosphodiesterases resulted in a prolongation of ttp, a flattering of the hyperpolarization maximum and an increase of the time constant of decay. It is suggested that a least three successive reactions are involved in the formation of ionic conductance channels after ACh receptor interaction. The results obtained with caffeine support the idea that formation of a cyclic nucleotide might participate in muscarinic action of ACh in the atrium.