Transient receptor potential-like channels mediate metabotropic glutamate receptor EPSCs in rat dopamine neurones.
Transient receptor potential (TRP) channels form cationic channels activated by diverse factors including mechanical stimuli, changes in osmolarity, pH and temperature, as well as the exogenous irritant, capsaicin. Metabotropic glutamate receptors have also recently been linked to TRP channel activation in neurones of the substantia nigra, hippocampus and cerebellum, suggesting a novel role for such channels in synaptic communication via endogenous neurotransmitters. We tested this for dopamine neurones in rat brain slices by characterizing the current-voltage relationship and pharmacology of EPSCs mediated by group I metabotropic glutamate receptor subtype 1 (mGluR1). Slow inward currents (273 +/- 35 pA peak amplitude, 381 +/- 25 ms latency, holding potential (V(h)) =-73 mV) representing evoked mGluR1 EPSCs were isolated in the presence of antagonists of AMPA, NMDA, GABA(A), GABA(B), muscarinic and glycine receptors. CPCCOEt (100 microM), an mGluR1 antagonist, blocked the residual EPSC in all recordings. mGluR1-activated EPSCs reversed polarity near -10 mV, consistent with the involvement of a cationic channel. Extracellular application of the non-selective TRP channel blockers SKF 96365, flufenamic acid and ruthenium red caused reversible inhibition of mGluR1-activated EPSCs. These characteristics parallel those of mGluR1 activation with an agonist and indicate the involvement of a TRP-like channel in mGluR1-mediated EPSCs.
Bengtson
C Peter
CP
Experimental Neurology Laboratory, IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179 Roma, Italy.
Tozzi
Alessandro
A
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects; D050052:TRPC Cation Channels
D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D050052:TRPC Cation Channels; C104077:metabotropic glutamate receptor type 1; D004298:Dopamine