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

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Abstract
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° 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 tot 3 wheret is time and displayed aQ 10 of about 12. The decay was less temperature-dependent (Q 10 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 flattening 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.