The effect of 2,4-dinitrophenol on electrical and mechanical activity, metabolism and ion movements in guinea-pig ventricular muscle.

1. DNP (2,4-dinitrophenol) reduced the duration of the action potential of guinea-pig ventricular muscle at a greater rate than did anoxia. The effect was dose-dependent and was modified by the concentration of glucose in the medium. DNP (0.1 mM) reduced the amplitude of the action potential of muscles incubated with 5 mM glucose; on raising the glucose concentration to 50 mM the effect was reversed.2. A large dose-dependent loss of K(+) occurred within 15 min of incubation with DNP and was attributed to increased efflux. K(+) loss was not related to Na(+) gain during the first 60 min of incubation; during the first 30 min DNP-treated muscle did not gain any Na(+). Although the shortening of the action potential by DNP during aerobic incubation was similar to that of muscles incubated under anaerobic conditions in glucose-free medium, the anaerobic incubation was not associated with increased (42)K efflux.3. It was concluded that the reduction in duration of the action potential was not necessarily the result of an increased K(+) efflux. The effect of DNP on (42)K efflux is considered to result from a direct effect on the cell membrane; the effect on electrical activity may be a combination of the increase in K(+) efflux and a reduction in the inward current due to Na(+) and Ca(++) previously assumed to be dependent on the glycolytic production of ATP.4. Electrogenic Na(+) pumping may contribute to the maintenance of resting potential in K(+)-depleted, DNP-treated cardiac muscle.