EFFECTS OF CATECHOLAMINES ON THE RESIDUAL SODIUM-CHANNEL DEPENDENT SLOW CONDUCTION IN GUINEA-PIG VENTRICULAR MUSCLES UNDER NORMOXIA AND HYPOXIA

Objective: The aim was to study the effects of catecholamines (isopren aline and noradrenaline) on the action potential upstroke and conducti on velocity in guinea pig ventricular papillary muscles. Methods: The upstroke velocity and the conduction velocity of the action potential were recorded by conventional two-microelectrode techniques in the gui nea pig Ventricular papillary muscle superfused with normoxic and hypo xic Tyrode solution of various potassium concentrations ([K+](0) 2.7-1 6.7 mM), stimulated at 0.2 Hz. Results: Under normoxic conditions, the upstroke of action potentials is composed of two components, dV/dt(ma x,fast) followed by dV/dt(max,slow,) when the muscle were perfused wit h relatively high [K+](0) (10.8-16.7 mM). The dV/dt(max,slow) is a mea sure of the residual (mostly inactivated) sodium current, while the dV /dt(max,slow) is a measure of calcium current. The conduction velocity at 13-17 mM [K+](0) ranged from 30-40 cm.s(-1) (slow conduction) with depolarised membrane potentials of about -60 mV. Isoprenaline in incr easing concentrations (0.01-1 mu M) did not significantly alter the co nduction velocity but altered the ionic channels responsible for the s low conduction from residual sodium channel to calcium channel. In the presence of D600 (2 mu M) or 1-verapamil (2.2 mu M), isoprenaline (0. 1 mu M) rapidly decreased dV/dt(max,fast) without increasing dV/dt(max ,slow,) and a conduction block occurred. In the presence of pindolol ( 2 mu M), all the effects of isoprenaline on dV/dt(max,fast,) dV/dt(max ,slow,) and conduction velocity were abolished. Noradrenaline had the same effects as isoprenaline, although the potency was much less. Unde r hypoxic conditions, the effects of catecholamines on the dV/dt(max,f ast) was the same as under normoxic conditions. Conclusions: Catechola mines alter the ionic channel responsible for the slow conduction of r eentry circuit from residual sodium to calcium channel, or vice versa, depending on the local concentrations of catecholamines. In the prese nce of a calcium antagonist, catecholamines strongly depress the (dV/d t(max,fast) dependent) slow conduction, leading to a complete block of conduction, under both normoxia and hypoxia.