Modification of "depressed fast channel dependent slow conduction" by lidocaine and verapamil in the presence or absence of catecholamines--evidence for alteration of preferential ionic channels for slow conduction.

We studied, with microelectrodes, the effect of lidocaine and 1-verapamil on the upstroke phase of action potentials and conduction velocity in incompletely depolarized ventricular papillary muscle (resting potential, -58 +/- 1 mV) perfused in a high K+ (16.7 mM) Tyrode's solution. The action potential upstroke had a slur and the maximum rate of rise (Vmax) consisted of 2 components: the first large (32 +/- 7 V/sec; Vmax,fast) and the second small (10 +/- 2 V/sec, Vmax,slow). The conduction velocity was slow and ranged about 30-35 cm/sec. Isoproterenol and noradrenaline increased Vmax,slow and decreased Vmax,fast, in a concentration dependent manner (10(-8) - 10(-5)M). These effects were abolished by following application of a beta-blocker, pindolol (1 microgram/ml). Thus, the dominant ionic channel responsible for the slow conduction seemed to alter from the depressed fast channel to the slow channel as the catecholamine concentration was increased. In the absence of isoproterenol, lidocaine (2 micrograms/ml) depressed Vmax with a resultant decrease of conduction velocity to 16.4 +/- 4.2 cm/sec and which was followed by a conduction block, while 1-verapamil was without effect. In the presence of isoproterenol (5 x 10(-7) M), 1-verapamil (1 microgram/ml) depressed the Vmax and decreased the conduction velocity to 16.9 +/- 4.2 cm/sec, just before development of the conduction block, while lidocaine was without effect. These results suggest that the dominant ionic channel responsible for the slow conduction in high K media (16.7 mM), can be readily altered by changes in extracellular catecholamine concentrations and that the slowest possible conduction velocity was approximately the same (about 16 cm/sec) between the depressed fast channel-dependent and the slow channel-dependent conductions. Clinical implications of these findings were discussed.