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

Abstract

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 ⁴²K 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 ⁴²K 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.