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 Ca(2+)-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.