L-type voltage-dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2-induced neuronal apoptosis

Snake venom group IA secretory phospholipase A2 (sPLA2-IA) is known as a neurotoxin. Snake venom sPLA2s are neurotoxic in vivo and in vitro, causing synergistic neurotoxicity to cortical cultures when applied with toxic concentrations of glutamate. However, it has not yet been cleared sufficiently how sPLA2-IA exerts neurotoxicity. Here, we found sPLA2-IA induced neuronal cell death in a concentration-dependent manner. This death was a delayed response requiring a latent time for 6 h. sPLA2-IA-induced neuronal cell death was accompanied with apoptotic blebbing, condensed chromatin, and fragmented DNA, exhibiting apoptotic features. NMDA receptor blockers suppressed the neurotoxicity of sPLA2-IA, but an AMPA receptor blocker did not. Interestingly, L-type voltage-dependent Ca2+ channel (L-VDCC) blocker significantly protected neurons from the sPLA2-IA-induced apoptosis. On the other hand, neither N-VDCC blockers nor P/Q-VDCC blocker did. In conclusion, we demonstrated that sPLA2-IA induced neuronal cell death via apoptosis. Furthermore, the present study suggests that not only NMDA receptor but also L-VDCC contributed to the neurotoxicity of snake venom sPLA2-IA.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (123 K)Download as PowerPoint slideHighlights► Secretory phospholipase A2-IA (sPLA2-IA) induced neuronal cell death via apoptosis. ► L-VDCC blockers rescued neurons from the sPLA2-IA-induced neuronal cell death. ► N- or P/Q-VDCC blockers did not rescue neurons from the neurotoxicity of sPLA2-IA. ► NMDA receptor blockers also attenuated the neurotoxicity of sPLA2-IA. ► AMPA/KA receptor did not contribute to the neurotoxicity of sPLA2-IA.