Acetylcholine induces overdrive excitation in sheep Purkinje fibres

The hypothesis that in the presence of acetylcholine overdrive may induce spontaneous repetitive activity (overdrive excitation) was tested by recording the transmembrane potentials and contractile force in sheep cardiac Purkinje fibres perfused in vitro. The results were: (a) acetylcholine 10(-8) to 10(-4) mol.litre-1 increased the action potential duration, the diastolic depolarisation slope and amplitude, and the twitch amplitude in a dose dependent manner; (b) at concentrations of 10(-5) to 10(-4) mol.litre-1 the interruption of a 60 beat.min-1 drive often induced repetitive spontaneous activity which was fastest immediately after the drive, slowed gradually, and ceased abruptly when an oscillatory potential failed to attain the threshold; (c) in the presence of acetylcholine, in quiescent preparations, applying drives of different durations and at different frequencies resulted in a steeper and larger diastolic depolarisation, oscillatory potentials, and a prolonged afterdepolarisation; (d) when overdrive excitation was induced it was faster and longer after faster or longer overdrives; (e) the cessation of overdrive was often associated with an aftercontraction; (f) in the presence of acetylcholine and a high extracellular calcium concentration (10.8 mmol.litre-1) overdrive excitation was preceded by a short period of inhibition; (g) strophanthidin (5 x 10(-8) mol.litre-1) facilitated acetylcholine induced overdrive excitation (without an initial inhibition); (h) lowering the extracellular sodium concentration (-50% NaCl) antagonised overdrive excitation; and (i) atropine 10(-5) mol.litre-1 prevented acetylcholine induced overdrive excitation. It is concluded that acetylcholine induces overdrive excitation by causing a larger diastolic depolarisation, oscillatory potentials, and a transient prolonged afterdepolarisation; that overdrive excitation requires sodium as a charge carrier underlying the electrical events leading to the attainment of the threshold; and that acetylcholine induces excitation by acting on a muscarinic receptor.