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 epi cardial, but not endocardial, APD and conflicting results regarding di rect vagal effects on the conduction system. In canine Purkinje fibers , we analyzed the action of the M(2) agonist oxotremorine (OXO, 0.1 mu M) on APD and on its cycle length (CL) dependence. Fibers were impale d with glass microelectrodes and superfused with Tyrode's solution. AP D(90) was measured after 3 minutes of drive at CL between 0.3 and 5 se conds. The best fit for the APD/CL relationship at steady state was a hyperbole: APD = APD(max) CL/(CL+CL(50)), where APD(max) (APD at infi nite CL) is a rate independent measure of APD, and CL(50) (CL at which 50% APD(max) is reached) is an index of the rate dependence of APD. I n 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 CL(50) 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 pretreate d with pertussis toxin (PTX). In conclusion, stimulation of M(2) recep tors in intact, and not PTX treated, Purkinje fibers affects APD but n ot its CL dependence. This may reflect the activation of a rate indepe ndent, background current through a GTP binding protein-linked pathway , such as, I-K,I-ACh. These data differ from those obtained in endocar dial and epicardial muscle, stressing the regional differences in vaga l modulation of ventricular electrophysiological properties.