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 store-operated Ca2+ 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 ofTRPC1 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.
Narayanan
K Lakshmi
KL
Interdisciplinary Centerfor Neurosciences (IZN), Department of Neuroanatomy, University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.
Irmady
Krithi
K
Subramaniam
Srinivasa
S
Unsicker
Klaus
K
von Bohlen und Halbach
Oliver
O
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism* / Q000633:toxicity; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D009924:Organ Culture Techniques; D034622:RNA Interference / Q000502:physiology; D050052:TRPC Cation Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D001896:Boron Compounds; D009498:Neurotoxins; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D018698:Glutamic Acid; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium