Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala.
Classical mammalian transient receptor potential channels form non-selective cation channels that open in response to activation of phospholipase C-coupled metabotropic receptors, and are thought to play a key role in calcium homeostasis in non-excitable cells. Within the nervous system transient receptor potential channels are widely distributed but their physiological roles are not well understood. Here we show that in the rat lateral amygdala transient receptor potential channels mediate an excitatory synaptic response to glutamate. Activation of group I metabotropic glutamate receptors on pyramidal neurons in the lateral amygdala with either exogenous or synaptically released glutamate evokes an inward current at negative potentials with a current voltage relationship showing a region of negative slope and steep outward rectification. This current is blocked by inhibiting G protein function with GTP-beta-S, by inhibiting phospholipase C or by infusing transient receptor potential antibodies into lateral amygdala pyramidal neurons. Using RT-PCR and Western blotting we show that transient receptor potential 1, transient receptor potential 4 and transient receptor potential 5 are present in the lateral amygdala. Single cell PCR confirms the presence of transient receptor potential 1 and transient receptor potential 5 in pyramidal neurons and we show by co-immunoprecipitation that transient receptor potential 1 and transient receptor potential 5 co-assemble as a heteromultimers in the amygdala. These results show that in lateral amygdala pyramidal neurons synaptically released glutamate activates transient receptor potential channels, which we propose are likely to be heteromultimeric channels containing transient receptor potential 1 and transient receptor potential 5/transient receptor potential 4.
Faber
E S L
ES
The Queensland Brain Institute, School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
Sedlak
P
P
Vidovic
M
M
Sah
P
P
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D018408:Patch-Clamp Techniques; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D050052:TRPC Cation Channels / Q000502:physiology*
D015220:Calcium Channels; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C503500:Trpc5 protein, rat; C104077:metabotropic glutamate receptor type 1; C096351:transient receptor potential cation channel, subfamily C, member 1; D012313:RNA