mu-Opioid receptor activation decreases N-type Ca2+ current in magnocellular neurons of the rat basal forebrain.
Opioid modulation of calcium currents was studied in acutely dissociated rat basal forebrain neurons using the whole cell patch-clamp recording technique. The mu-opioid receptor agonist DAGO reversibly suppressed high-voltage activated calcium currents and slowed their rate of activation, while neither delta- nor kappa-opioid receptor agonists were effective in modifying calcium current in these neurons. The inhibitory effect of DAGO on calcium current was abolished following irreversible blockade of N-type calcium channels by omega-conotoxin GVIA, whereas DAGO-induced inhibitory responses were not affected following blockade of L-type calcium channels by nifedipine. These findings indicate that mu-opioid receptors are negatively coupled to N-type calcium channels on the postsynaptic membrane of basal forebrain neurons. Calcium currents recorded from a significant number of large, mu-opioid sensitive neurons were also suppressed by muscarinic receptor activation, while smaller, mu-opioid sensitive neurons were not sensitive to muscarinic receptor activation. Thus, the present data demonstrate that voltage-activated calcium influx in several subpopulations of basal forebrain neurons can be regulated by mu-opioid receptor activation. These results suggest that mu-opioid regulation of calcium current may be an important functional mechanism in regulating neuronal excitability and synaptic transmission in the basal forebrain.
Soldo
B L
BL
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA. soldob@umich.edu
Moises
H C
HC
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D016548:Prosencephalon / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D015220:Calcium Channels; D004745:Enkephalins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-