Voltage dependence of β-adrenergic modulation of conduction in the canine Purkinje fiber

Although recent voltage-clamp and microelectrode studies have demonstrated β-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 β-adrenergic agonist, the effect of 1 μmol/L isoproterenol on impulse propagation in canine Purkinje fibers was examined by using a dual-microelectrode technique. At physiological membrane potentials ([K⁺](o) 5.4 mmol/L), isoproterenol increased squared conduction velocity (θ, 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 (V̇(max), 641±50 versus 657±47 V/s, P=NS). At transmembrane potential of -65 mV, produced by 12 mmol/L [K⁺](o) titration, θ² declined 79% to 0.73±0.44 (m/s)² as V̇(max) decreased 85% to 95±43 V/s (P<.02). The addition of isoproterenol further decreased θ² to 0.49±0.33 (m/s)² (P=.02) in parallel with a further decline in V̇(max) to 51±25 V/s (P<.05). Isoproterenol produced a 3-mV hyperpolarizing shift of apparent Na⁺ channel availability curves generated from both θ² and V̇(max), used as indexes of the fast inward I(Na), without changing the slopes of the relation. The relation between normalized θ² and V̇(max) over a range of depolarized potentials was linear and was not appreciably altered by isoproterenol. These data suggest that β-adrenergic modulation of conduction is voltage dependent and follows comparable changes in I(Na) to the extent reflected by V̇(max). In partially depolarized canine Purkinje fibers, isoproterenol slows conduction and reduces V̇(max), which may contribute to arrhythmogenesis during myocardial ischemia.