title: Involvement of transient receptor potential-like channels in responses to mGluR-I activation in midbrain dopamine neurons.
abstract: We investigated the involvement of store-operated channels (SOCs) and transient receptor potential (TRP) channels in the response to activation of the group I metabotropic glutamate receptor subtype 1 (mGluR1) with the agonist (S)-3,5-dihydroxyphenylglycine (DHPG, puff application) in dopamine neurons in rat brain slices. The mGluR1-induced conductance reversed polarity close to 0 mV and at more positive potentials when extracellular potassium concentrations were increased, indicating the involvement of a cationic channel. DHPG currents but not intracellular calcium responses were reduced by low extracellular sodium concentrations but were not affected by sodium channel blockers, tetrodotoxin and saxitoxin or by inhibition of the h-current with cesium. Abolition of calcium responses with intracellular BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 10 mm) did not affect current responses, indicating they were not calcium activated. Extracellular application of non-selective SOCs and TRP channel blockers 2-aminoethoxydiphenylborane (2-APB), SKF96365, ruthenium red and flufenamic acid (but not gadolinium) reduced DHPG current and calcium responses. Intracellular application of ruthenium red and 2-APB did not affect DHPG currents, indicating that IP3 and ryanodine receptors did not mediate their actions. Single-cell PCR revealed the presence of TRPC1 and 5 mRNA in most dopamine neurons and subtypes 3, 4 and 6 in some. Store depletion evoked calcium entry indicative of SOCs, providing the first functional observation of such channels in native central neurons. Store depletion with either cyclopiazonic acid or ryanodine abolished calcium but not current responses to DHPG. The electrophysiological and pharmacological properties of the mGluR1-induced inward current are consistent with the involvement of TRP channels whereas calcium responses are dependent on the function of SOCs in voltage clamp recordings.
authors: Experimental Neurology Laboratory, I.R.C.C.S. Fondazione Santa Lucia Via Ardeatina 306, Rome, Italy.
authors: Alessandro
authors: A
authors: Tozzi
authors: C Peter
authors: CP
authors: Bengtson
authors: Patrizia
authors: P
authors: Longone
authors: Corrado
authors: C
authors: Carignani
authors: Francesca R
authors: FR
authors: Fusco
authors: Giorgio
authors: G
authors: Bernardi
authors: Nicola B
authors: NB
authors: Mercuri
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D002148:Calmodulin-Binding Proteins; D018756:GABA Antagonists; D018094:Receptors, Metabotropic Glutamate; D050051:Transient Receptor Potential Channels; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D004298:Dopamine