Influence of procainamide on sodium and potassium exchange and permeabilities in cultured human cells.

The effect of procainamide on membrane cation exchange was investigated using monolayer cultures of Girardi heart cells. The initial effect of procainamide (10(-6) to 10(-3) mol/litre) was to produce a prompt reduction of the passive Na influx, dose-dependent along a sigmoid log dose-response curve. This effect was complete within 3 min and thereafter showed no further time-dependent increase. Mean passive Na influx (pmol-cm-2/s) decreased from 19.1 to 17.7 (P less than 0.05) and 10.4 (P less than 0.001) in 10(-5) and 10(-3) mol/litre procainamide, respectively. No effect on active Na extrusion was noted before 3 min following exposure to the drug, after which time it progressively declined reaching a minimum value for each concentration by 6 min and remaining at this level throughout a further 60 min exposure. For each concetnration this minimum value was similar to the Na influx measured under identical conditions. Na-coupled active K influx showed a parallel pattern of inhibition. K efflux was not decreased until approximately 20 min following exposure to the drug, but once present the reduction was similar in magnitude to that in the correspondingly measured K influx. Kinetic flux analysis revealed a decrease in both PNa and PK but indicated a greater effect on PNa. The results suggest that all of the above effects could be explained on the basis of one direct action of the drug, namely, the prompt initial decrease in PNa and Na influx. All other effects noted, both active and passive, could then be secondary to this phenomenon.