Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death

Massive neuronal activation by glutamate can result in an excessive rise in cytoplasmic calcium, a process ultimately leading to neuronal death. We have investigated the role of the transient receptor potential channel 1 (TRPC1) in mediating glutamate-induced neuron death. We show that 2-APB (a blocker of storeoperated Ca(2+) entry) dramatically reduces glutamate-induced cell death in hippocampal organotypic slice cultures and that glutamate-induced toxicity is accompanied by an increase in TRPC1 expression. RNAi mediated knock-down of TRPC1 in slice cultures prevented glutamate-induced cell death, indicating that TRPC1 plays a prominent role in calcium entry following exposure to glutamate. Thus, TRPC1 may represent a promising target for pharmacological interventions to prevent or reduce glutamate-induced neuronal damage. (c) 2008 Elsevier Ireland Ltd. All rights reserved.