Involvement of apoptosis and calcium accumulation through TRPV1 channels in neurobiology of epilepsy

Possible molecular pathways of involvement of apoptosis and calcium accumulation through TRPV1 channels in hippocampal and DRG neurons of epileptic rats. Convulsions in epilepsy can results in augmented glutamate release, leading to Ca2+ uptake through NMDA receptor and TRP channels. Mitochondria were reported to accumulate Ca2+ provided intracellular Ca2+ rises, thereby leading to depolarization of mitochondrial membranes. At the extreme, Ca2+ entry causes severe mitochondrial permeability transition (MPT) or even the rupture of the mitochondrial membrane, substantial swelling of the mitochondria with rupture of the outer membrane and release of apoptosis-inducing factors such as caspase 3 and 9. Capsaicin and ROS activates via desensitization of TRPV1 channels although pharmacological desensitization of TRPV1 channels through antagonists such as capsazepine (CPZ) and 5′-iodoresiniferatoxin (IRTX) contributes to an immediate reduction on neuronal excitability. ROS enhances also spontaneous release of glutamate from presynaptic terminals onto neurons through TRPV1 channel activation. The molecular pathway may be a cause of epileptic seizures and the subject should urgently investigate.116