| Summary: | Abstract Background Intracellular Ca2+ overload induced by extracellular Ca2+ entry has previously been confirmed to be an important mechanism for the cardiotoxicity as well as the acute heart dysfunction induced by jellyfish venom, while the underlying mechanism remains to be elucidated. Methods Under extracellular Ca2+-free or Ca2+-containing conditions, the Ca2+ fluorescence in isolated adult mouse cardiomyocytes pre-incubated with tentacle extract (TE) from the jellyfish Cyanea capillata and β blockers was scanned by laser scanning confocal microscope. Then, the cyclic adenosine monophosphate (cAMP) concentration and protein kinase A (PKA) activity in primary neonatal rat ventricular cardiomyocytes were determined by ELISA assay. Furthermore, the effect of propranolol against the cardiotoxicity of TE was evaluated in Langendorff-perfused rat hearts and intact rats. Results The increase of intracellular Ca2+ fluorescence signal by TE was significantly attenuated and delayed when the extracellular Ca2+ was removed. The β adrenergic blockers, including propranolol, atenolol and esmolol, partially inhibited the increase of intracellular Ca2+ in the presence of 1.8 mM extracellular Ca2+ and completely abolished the Ca2+ increase under an extracellular Ca2+-free condition. Both cAMP concentration and PKA activity were stimulated by TE, and were inhibited by the β adrenergic blockers. Cardiomyocyte toxicity of TE was antagonized by β adrenergic blockers and the PKA inhibitor H89. Finally, the acute heart dysfuction by TE was antagonized by propranolol in Langendorff-perfused rat hearts and intact rats. Conclusions Our findings indicate that β adrenergic receptor/cAMP/PKA signaling contributes to the intracellular Ca2+ overload through intracellular Ca2+ release by TE from the jellyfish C. capillata.
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