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 (isoprenaline and noradrenaline) on the action potential upstroke and conduction 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 guinea pig ventricular papillary muscle superfused with normoxic and hypoxic Tyrode solution of various potassium concentrations ([K+]o 2.7-16.7 mM), stimulated at 0.2 Hz.

RESULTS

Under normoxic conditions, the upstroke of action potentials is composed of two components, dV/dtmax,fast followed by dV/dtmax,slow, when the muscle were perfused with relatively high [K+]o (10.8-16.7 mM). The dV/dtmax,fast is a measure of the residual (mostly inactivated) sodium current, while the dV/dtmax,slow is a measure of calcium current. The conduction velocity at 13-17 mM [K+]o ranged from 30-40 cm.s-1 (slow conduction) with depolarised membrane potentials of about -60 mV. Isoprenaline in increasing concentrations (0.01-1 microM) did not significantly alter the conduction velocity but altered the ionic channels responsible for the slow conduction from residual sodium channel to calcium channel. In the presence of D600 (2 microM) or 1-verapamil (2.2 microM), isoprenaline (0.1 microM) rapidly decreased dV/dtmax,fast without increasing dV/dtmax,slow and a conduction block occurred. In the presence of pindolol (2 microM), all the effects of isoprenaline on dV/dtmax,fast, dV/dtmax,slow, and conduction velocity were abolished. Noradrenaline has the same effects as isoprenaline, although the potency was much less. Under hypoxic conditions, the effects of catecholamines on the dV/dtmax,fast was the same as under normoxic conditions.

CONCLUSIONS

Catecholamines alter the ionic channel responsible for the slow conduction of reentry circuit from residual sodium to calcium channel, or vice versa, depending on the local concentrations of catecholamines. In the presence of a calcium antagonist, catecholamines strongly depress the (dV/dtmax,fast dependent) slow conduction, leading to a complete block of conduction, under both normoxia and hypoxia.