Inhibition of calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activity by dimethyl sulfoxide

Membrane-bound (Ca2+ + Mg2+)-ATPase activity from human erythrocyte white ghosts in the calmodulin-activated state was inhibited by DMSO in concentrations of 3% (v/v) and above. At 10%, DMSO inhibited calmodulin activation by 47.7%, while basal, calmodulin-independent (Ca2+ + Mg2+)-ATPase and (Mg2+)-ATPase activity remained unaffected. (Na+ + K+)-ATPase activity was also reduced but exhibited a greater IC50. Concentration-effect analyses showed the inhibition by 10% DMSO to be a reversible, non-competitive effect with regard to calmodulin, Ca2+, and substrate activation. Calmodulin-stimulated processes may be more susceptible to inhibition by DMSO than related enzymatic catalysis, and thus may help explain the multitude of reported cellular events caused by the solvent. Furthermore, DMSO affected membrane-associated enzymatic mechanisms opposite to those reported for purified enzyme outside its native membrane environment.