Force-relaxant Actions of Dimethyl Sulfoxide on Guinea-pig and Rabbit Papillary Muscles

Recent voltage-clamp analysis of dimethyl sulfoxide (DMSO; 0.1–10% v/v) action on membrane currents in guinea-pig ventricular myocytes (strong inhibition of delayed-rectifier K+current, inhibition of Na+pump current, little effect on L-type Ca2+current) suggested that the solvent would have a strong positive inotropic effect on guinea-pig papillary muscles. In muscles driven at 1 Hz, the major effects of 30 min superfusion with hyperosmotic 10% DMSO were: (1) a 33% lengthening of the action potential duration; (2) a 23% depression of developed tension; and (3) a pronounced positive inotropy on washout of the solvent. Osmotic change in cell volume was a possible reason for these effects; however, hyperosmotic sucrose solution that shrunk myocyte volume by a DMSO-like 12% failed to elicit the DMSO response. It was postulated that DMSO has both stimulatory and inhibitory actions: during treatment the stimulatory component (Ca2+accumulation due to action potential lengthening and Na+pump inhibition) is masked by a concomitant inhibition of Ca2+-myofilament interaction; removal of the solvent reveals the Ca2+overload. In support of this interpretation, (1) DMSO depressed developed tension by up to 85% when the stimulatory influence was attenuated by eliminating action potential lengthening (rabbit papillary muscles), relieving pump inhibition (elevated K+), or preloading Ca2+(low-K+or low-Na+superfusate), and (2) DMSO relaxed Na+-free contractures, and nearly abolished caffeine-induced contractures, in quiescent guinea-pig muscles. These data suggest that DMSO has a reversible, powerful inhibitory action on the myofilament force-generating machinery.