On the binding of zinc and mersalyl to the contractile element in muscle and the relation to its relaxing effect.

In order to elucidate the functionally relevant coupling of zinc and mersalyl with the contractile element in muscle, a comparative study of their relaxing (or contraction-inhibiting) effects on glycerol-extracted rabbit psoas fibres as concerns reversibility, pH-dependence and synergism has been performed, as well as determinations of the uptake of zinc and mersalyl by the fibres after immersion in subtotal, functionally equivalent concentrations of the metals. Zinc and mersalyl have about the same affinity for the functional sites. There is additive synergism between the zinc and mersalyl effects, as tested at different pH-levels, indicating that zinc and mersalyl act by blocking the same functional groups, probably SH-groups, in the contractile element. However, while the zinc-induced effect is strongly dependent on the pH between 6.0 and 8.0, no pH-dependence at all is found for the mersalyl effect in this pH-range. Evidently zinc and mersalyl combine with the functional groups in a different way, mersalyl conceivably by simple coupling, zinc, however, only after entering into a chelate formation, in which unprotonated groups with a pK-value of about 6.7, probably imidazole groups, have to be included.