VOLTAGE-DEPENDENCE OF BETA-ADRENERGIC MODULATION OF CONDUCTION IN THE CANINE PURKINJE-FIBER

Although recent voltage-clamp and microelectrode studies have demonstrated beta-adrenergic modulation of Na+ current (I-Na) the modulation of conduction by catecholamines and the voltage dependence of that process have not been elucidated. To determine whether voltage-dependent modulation of conduction occurs in the presence of a beta-adrenergic agonist, the effect of 1 mu mol/L isoproterenol on impulse propagation in canine Purkinje fibers was examined by using a dual-microelectrode technique. At physiological membrane potentials ([K-t](o) 5.4 mmol/L), isoproterenol increased squared conduction velocity [theta(2), 0.39 +/- 0.25 (m/s)(2) (mean+/-SD)] from 3.46+/-0.86 to 3.85+/-0.98 (m/s)(2) (P<.011), an 11% change, without altering the maximum first derivative of the upslope of phase 0 of the action potential (V-max 641+/-50 versus 657+/-47 V/s, P=NS). At transmembrane potential of -65 mV, produced by 12 mmol/L [K+](o) titration, theta(2) declined 79% to 0.73+/-0.44 (m/s)(2) as V-max decreased 85% to 95+/-43 V/s (P<.02). The addition of isoproterenol further decreased theta(2) to 0.49 +/- 0.33 (m/s)(2) (P=.02) in parallel with a further decline in V-max to 51+/-25 V/s (P<.05). Isoproterenol produced a 3-mV hyperpolarizing shift of apparent Na+ channel availability curves generated from both theta(2) and V-max, used as indexes of the fast inward I-Na, without changing the slopes of the relation. The relation between normalized theta(2) and V-max over a range of depolarized potentials was linear and was not appreciably altered by isoproterenol. These data suggest that beta-adrenergic modulation of conduction is voltage dependent and follows comparable changes in I-Na to the extent reflected by V-max. In partially depolarized canine Purkinje fibers, isoproterenol slows conduction and reduces V-max, which may contribute to arrhythmogenesis during myocardial ischemia.