Influence of calmodulin antagonists on Ca²⁺transport in the lens

Attempts were made to elucidate the relation between lens opacification resulting from inhibition of Ca²⁺transport and high calcium accumulation in the lens. Mouse lenses were incubated with naphthalenesulfonamide compounds (W-5, W-7, W-12 and W-13) which act as calmodulin antagonists. When lens Ca²⁺-ATPase activity was inhibited by those calmodulin antagonists, an accumulation of calcium in the lens was observed. This phenomenon depended on the chemical structure of calmodulin antagonist. In lenses treated with W-7, more than 97% of excess calcium was bound. Insoluble protein increased from 8.5 to 17% of the total protein and the degree of lens opacification increased to 85.1%. These results suggested that dysfunction of the Ca-pump system leads to calcium accumulation, thus in turn inducing protein dénaturation which in turn is followed by lens opacification.