Isolated Rat Cardiomyocytes Differ in Their Sensitivity to the Action of Heterodimeric Phospholipase A2 from the Venom of the Viper Vipera nikolskii

Snake venom phospholipase A2 (PLA2) affect, among others, the cardiovascular system; however, data on their effect on isolated cardiomyocytes are practically absent. In this work, we investigated the influence of HDP-1 and HDP-2, heterodimeric PLA2s from the venom of viper Vipera nikolskii, on isolated rat cardiomyocytes. Cardiomyocytes were stained with fluorescent probes and fluorescence was measured using Cell Observer fluorescent station. After PLA2 application, there was a prolonged lag phase with no changes in cell morphology or probe signal, followed by fluctuations in the cytosolic calcium level and cell hypercontracture with subsequent disruption of plasma membrane. In individual cardiomyocytes, time from the toxin addition until the hypercontracture varied by more than two-fold. In experiments with electrical stimulation, at HDP-2 application, a “pause” in contractions was observed, characterized by a decrease in the amplitude of the fluorescent response. Then, the contraction rhythm recovered, and later, hypercontracture was observed followed by cell destruction. Depending on times to these events, all cardiomyocytes studied were classified into two groups with fast and slow response to PLA2 action. The observed differences in the sensitivity of cardiomyocytes may be explained by unequal concentrations of intracellular calcium due to the different states of the cells at isolation.