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 A(2) (sPLA(2)-IA) is known as a neurotoxin. Snake venom sPLA(2)s 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 sPLA(2)-IA exerts neurotoxicity. Here, we found sPLA(2)-IA induced neuronal cell death in a concentration-dependent manner. This death was a delayed response requiring a latent time for 6 h. sPLA(2)-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 sPLA(2)-IA, but an AMPA receptor blocker did not. Interestingly, L-type voltage-dependent Ca2+ channel (L-VDCC) blocker significantly protected neurons from the sPLA(2)-IA-induced apoptosis. On the other hand, neither N-VDCC blockers nor P/Q-VDCC blocker did. In conclusion, we demonstrated that sPLA(2)-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 sPLA(2)-IA. (C) 2013 Elsevier Inc. All rights reserved.