The role of TRPC6 in seizure susceptibility and seizure-related neuronal damage in the rat dentate gyrus

• TRPC6 plays an important role in neuronal activity and neuronal survivals.
• TRPC6 expression was down-regulated in the dentate gyrus in epileptic rats.
• TRPC6 knockdown increased seizure susceptibility in the rat dentate gyrus.
• TRPC6 knockdown promoted programed necrosis in dentate granule cells following SE.
• TRPC6 may inhibit seizure susceptibility and SE-induced neuronal damage.

Transient receptor potential canonical channel-6 (TRPC6) forms Ca2+-permeable non-selective cation channels in neurons. Although TRPC6 plays an important role in neurite outgrowth and neuronal survival during development, TRPC6 expression profiles available to identify distinctive hippocampal neuronal damage and hippocampal excitability in epilepsy are less defined. As compared to normal animals, TRPC6 expression was down-regulated in chronic epileptic rats showing spontaneous recurrent seizures. TRPC6 knockdown increased seizure susceptibility, excitability ratio and paired-pulse inhibition in the dentate gyrus (DG) of normal animals. Furthermore, TRPC6 knockdown promoted programed neuronal necrosis in dentate granule cells, but prevented it in CA1 and CA3 neurons following status epilepticus. The present data suggest for the first time that TRPC6 may inhibit seizure susceptibility and neuronal vulnerability in the rat DG.