Muscarinic Effects on Action Potential Duration and its Rate Dependence in Canine Purkinje Fibers

Studies of the autonomic influence on action potential duration (APD) in the ventricles show direct effects of muscarinic stimulation on epicardial, but not endocardial, APD and conflicting results regarding direct vagal effects on the conduction system. In canine Purkinje fibers, we analyzed the action of the M₂ agonist oxotremorine (OXO, 0.1μM) on APD and on its cycle length (CL) dependence. Fibers were impaled with glass microalectrodes and superfused with Tyrode s solution. APD₉₀ was measured after 3 minutes of drive at CL between 0.3 and 5 seconds. The best fit for the APD/CL relationship at steady state was a hyperbole: APD = APD_max*CL/(CL+CL₅₀), where APD_max (APD at infinite CL) is a rate independent measure of APD, and CL₅₀ (CL at which 50% APD_max is reached) is an index of the rate dependence of APD. In five fibers, OXO reduced APD at all CL (P < 0.05), APD_max was also reduced to 377 ± 41 ms from 447 ± 34 ms (P < 0.05), while CL₅₀ was unchanged (405 ± 46 ms from 437 ± 28 ms). No effects of OXO on APD and APD_max were seen in two fibers obtained from dogs pretreated with pertussis toxin (PTX). In conclusion, stimulation of M₂ receptors in intact, and not PTX treated, Purkinje fibers affects APD but not its CL dependence. This may reflect the activation of a rate independent, background current through a GTP binding protein-linked pathway, such as, I_K.ACH These data differ from those obtained in endocardial and epicardial muscle, stressing the regional differences in vagal modulation of ventricular electrophysiological properties.