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

K Lakshmi Narayanan; Krithi Irmady; Srinivasa Subramaniam; Klaus Unsicker; Oliver von Bohlen und Halbach

doi:10.1016/j.neulet.2008.09.034

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

Neurosci Lett. 2008 Dec 3;446(2-3):117-22. doi: 10.1016/j.neulet.2008.09.034.

Authors

K Lakshmi Narayanan¹, Krithi Irmady, Srinivasa Subramaniam, Klaus Unsicker, Oliver von Bohlen und Halbach

Affiliation

¹ Interdisciplinary Centerfor Neurosciences (IZN), Department of Neuroanatomy, University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.

PMID: 18822346
DOI: 10.1016/j.neulet.2008.09.034

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Atrophy / genetics
Atrophy / metabolism
Atrophy / physiopathology
Boron Compounds / pharmacology
Calcium / metabolism
Calcium Signaling / drug effects
Calcium Signaling / physiology*
Cell Death / drug effects
Cell Death / physiology
Down-Regulation / drug effects
Down-Regulation / genetics
Glutamic Acid / metabolism*
Glutamic Acid / toxicity
Hippocampus / metabolism*
Hippocampus / pathology
Hippocampus / physiopathology
Mice
Mice, Inbred C57BL
Nerve Degeneration / chemically induced
Nerve Degeneration / metabolism*
Nerve Degeneration / physiopathology
Neurodegenerative Diseases / genetics
Neurodegenerative Diseases / metabolism
Neurodegenerative Diseases / physiopathology
Neurons / drug effects
Neurons / metabolism
Neurons / pathology
Neurotoxins / metabolism*
Neurotoxins / toxicity
Organ Culture Techniques
RNA Interference / physiology
TRPC Cation Channels / drug effects
TRPC Cation Channels / genetics
TRPC Cation Channels / metabolism*

Substances

Boron Compounds
Neurotoxins
TRPC Cation Channels
transient receptor potential cation channel, subfamily C, member 1
Glutamic Acid
2-aminoethoxydiphenyl borate
Calcium