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 dissociat ed rat basal forebrain neurons using the whole cell patch-clamp record ing technique. The mu-opioid receptor agonist DAGO reversibly suppress ed high-voltage activated calcium currents and slowed their rate of ac tivation, while neither delta- nor kappa-opioid receptor agonists were effective in modifying calcium current in these neurons. The inhibito ry effect of DAGO on calcium current was abolished following irreversi ble blockade of N-type calcium channels by omega-conotoxin GVIA, where as DAGO-induced inhibitory responses were not affected following block ade of L-type calcium channels by nifedipine. These findings indicate that mu-opioid receptors are negatively coupled to N-type calcium chan nels on the postsynaptic membrane of basal forebrain neurons. Calcium currents recorded from a significant number of large, mu-opioid sensit ive neurons were also suppressed by muscarinic receptor activation, wh ile smaller, mu-opioid sensitive neurons were not sensitive to muscari nic receptor activation. Thus, the present data demonstrate that volta ge-activated calcium influx in several subpopulations of basal forebra in neurons can be regulated by mu-opioid receptor activation. These re sults suggest that mu-opioid regulation of calcium current may be an i mportant functional mechanism in regulating neuronal excitability and synaptic transmission in the basal forebrain.