An effect of the cardiotoxic protein volvatoxin a on the function and structure of heart muscle cells

Volvatoxin-A, the heat labile cardiotoxin present in the mushroom Volvariella volvacea, causes a competitive, dose and time-dependent inhibition of the Ca²⁺-accumulating activity of a sarcoplasmic-reticulum rich microsomal fraction isolated from guinea pig ventricular muscle. The inhibition is accompanied by an activation of the Ca²⁺-dependent ATPase enzyme. Concentrations of toxin which inhibit the Ca²⁺-transporting activity of the microsomes render them leaky to Ca²⁺, but do not effect the rate of incorporation of P³². Ten μg/ml toxin failed to alter the activity of the Na⁺ + K⁺-activated, ouabain sensitive ATPase enzyme. It damaged the fine morphology of the mitochondria, inhibited the ability of isolated mitochondria to accumulate Ca²⁺, and had little effect on the ability of isolated plasma membranes to bind Ca²⁺. These findings may explain why volvatoxin A increases the diastolic resting tension in heart muscle.