In the electrically driven ventricular muscle (twitch response) of the bullfrog, N-ethylmaleimide (NEM, 10
-5 to 10
-3M) caused a dose-dependent positive inotropic action (PIA). The NEM-induced PIA was reduced by pretreatment with verapamil (10
-5M) and MnCl2 (10
-3M) and was blocked by pre-treatment with 1-cysteine (2×10
-3M). Ouabain (OU) produced a moderate PIA followed by a negative inotropic action (NIA) concomitant with a marked elevation of the resting tension. The OU-induced PIA at high concentrations (10
-5 and 10
-4M) was significantly reduced only by verapamil. The PIA induced by either NEM or OU was hardly affected by propranolol. OU produced a greater inhibition of Na
+-K
+ ATPase activity of cell membranes isolated from the ventricular muscle than that of NEM without affecting Mg
2+ dependent ATPase activity. Both NEM and isoprenaline but not OU restored the twitch response which disappeared in the potassium (20 mM K
+)-depolarized muscle. The twitch response restored by NEM was abolished by the calcium antagonists, MnCl2 and verapamil and 1-cysteine but not by propranolol. The twitch response restored by isoprenaline was blocked by the calcium antagonists and propranolol but not by 1-cysteine. These results suggest that the NEM-induced PIA may result from the increased calcium influx into the muscle. The results also suggest that the mechanism of the NEM-induced PIA is discrete from that of the OU-induced PIA.
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