D1-like dopamine receptors selectively block P/Q-type calcium channels to reduce glutamate release onto cholinergic basal forebrain neurones of immature rats.
Whole-cell patch-clamp recordings of non-NMDA glutamatergic EPSCs were made from identified cholinergic neurones in slices of basal forebrain (BF) of young rats (P13-P18), to investigate the subtypes of calcium channels involved in dopamine D(1)-like receptor-mediated presynaptic inhibition of the EPSCs. The BF cholinergic neurones were pre-labelled by intracerebroventricular injection of a fluorescent marker, Cy3-192IgG. A D(1)-like receptor agonist, SKF 81297 (30 microM) suppressed the EPSCs reversibly by about 30%, and this inhibition was reproducible. Calcium channel subtypes involved in the glutamatergic transmission were elucidated using selective Ca(2+) channel blockers. The N-type Ca(2+) channel blocker omega-conotoxin (omega-CgTX, 3 microM) suppressed the EPSCs by 57.5%, whereas the P/Q-type channel selective blocker omega-agatoxin-TK (omega-Aga-TK, 200 nM) suppressed the EPSCs by 68.9%. Simultaneous application of both blockers suppressed the EPSCs by 96.1%. The R-type Ca(2+) channel blocker SNX-482 (300 nM) suppressed the EPSCs by 18.4%, whereas nifedipine, the L-type Ca(2+) channel blocker (10 microM), had little effect. In the presence of omega-Aga-TK, SKF 81297, a dopamine D(1)-like receptor agonist, had no effect on the EPSCs. On the other hand, SKF 81297 could still inhibit the EPSCs in the presence of either omega-CgTX, SNX-482 or nifedipine. SKF 81297 had no further effect on the EPSCs when external Ca(2+) concentration was raised to 7.2 mM in the presence of omega-Aga-TK, but could still inhibit the EPSCs in high Ca(2+) solution after omega-CgTX application. Forskolin (FK, 10 microM), an activator of adenylyl cyclase pathway, suppressed the EPSCs, and the FK-induced effect was mostly blocked in the presence of omega-Aga-TK but not that of omega-CgTX. These results suggest that D(1)-like receptor activation selectively blocks P/Q-type calcium channels to reduce glutamate release onto BF cholinergic neurones.
Momiyama
Toshihiko
T
Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan. tmomi@nips.ac.jp
Fukazawa
Yugo
Y
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000187:drug effects*; D020907:Calcium Channels, Q-Type / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism*; D007276:Injections, Intraventricular; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects*
D001552:Benzazepines; D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D005456:Fluorescent Dyes; D020800:Receptor, Nerve Growth Factor; D017447:Receptors, Dopamine D1; D005576:Colforsin; D018698:Glutamic Acid; C067113:SK&F 81297; D002795:Choline O-Acetyltransferase