The response of single cardiac sodium channels in neonatal rats to the dihydropyridines CGP 28392 and (-)-Bay K 8644.

Cell-attached patch clamp recording of elementary Na+ currents were performed at 19 degrees C in neonatal cultured rat heart cells to study Na+ channel properties in the presence of dihydropyridines. Bath application of racemic CGP 28392, at 5 mumol/l, activated Na+ channels. By increasing the open probability, P0, and/or the number of functioning Na+ channels, peak INa in reconstructed macroscopic Na+ currents rose without changes in the decay kinetics. This was accompanied by a prolongation of open time. (-)-Bay K 8644 (1-10 mumol/l) had the same effect. In the presence of either agonist, Na+ channels retained an uniform open state and, as estimated from the mean number of openings per sequence, their initial tendency to reopen. Rarely appearing ultralong opening sequences are unlikely to be drug-induced as Na+ channels can likewise switch into this particular activity mode under drug-free conditions. Racemic CGP 28392, at 50 mumol/l, blocked Na+ channels in an all-or-none fashion suggesting that one enantiomer acts as agonist and the other enantiomer as blocker. A quite different response consisting of the occurrence of a second open state with a several-fold increased life time and a significantly increased reopening was observed with (-)-Bay K 8644 in damaged cardiocytes with hyperpermeable membranes and after patch excision into drug-containing solution. Evidence was obtained from control inside-out patches that this increased reopening is most probably caused by the solvent, ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)