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Group I metabotropic glutamate receptor‐dependent TRPC channel trafficking in hippocampal neurons
Author(s) -
Wang Min,
Bianchi Riccardo,
Chuang ShihChieh,
Zhao Wangfa,
Wong Robert K. S.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04377.x
Subject(s) - trpc , trpc5 , transient receptor potential channel , metabotropic glutamate receptor , chemistry , glutamate receptor , pharmacology , receptor , biochemistry , biology
The group I metabotropic glutamate receptor agonist ( S )‐3,5‐dihydroxyphenylglycine (DHPG) elicited two phases of synchronized neuronal (epileptiform) discharges in hippocampal slices: an initial phase of short duration discharges followed by a phase of prolonged discharges. We assessed the involvement of transient receptor potential canonical (TRPC) channels in these responses. Pre‐treatment of hippocampal slices with TRPC channel blockers, 1‐[beta‐[3‐(4‐methoxyphenyl)propoxy]‐4‐methoxyphenethyl]‐1H‐imidazole hydrochloride (SKF96365) or 2‐aminoethoxydiphenyl borate, did not affect the short epileptiform discharges but blocked the prolonged epileptiform discharges. SKF96365 suppressed ongoing DHPG‐induced prolonged epileptiform discharges. Western blot analysis showed that the total TRPC4 or TRPC5 proteins in hippocampal slices were unchanged following DHPG. DHPG increased TRPC4 and TRPC5 in the cytoplasmic compartment and decreased these proteins in the plasma membrane. Translocation of TRPC4 and TRPC5 was suppressed when the epileptiform discharges were blocked by ionotropic glutamate receptor blockers. Translocation of TRPC4 and TRPC5 was also prevented in slices from phospholipase C (PLC) β1 knockout mice, even when synchronized discharges were elicited by the convulsant 4‐aminopyridine. The results suggest that TRPC channels are involved in generating DHPG‐induced prolonged epileptiform discharges. This function of TRPC channels is associated with a neuronal activity‐ and PLCβ1‐dependent translocation of TRPC4 and TRPC5 proteins from the plasmalemma to the cytoplasmic compartment.