μ-Opioid receptor activation decreases N-type Ca 2+ current in magnocellular neurons of the rat basal forebrain

Abstract

Opioid modulation of calcium currents was studied in acutely dissociated rat basal forebrain neurons using the whole cell patch-clamp recording technique. The μ-opioid receptor agonist DAGO reversibly suppressed high-voltage activated calcium currents and slowed their rate of activation, while neither δ- nor κ-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 ω-conotoxin GVIA, whereas DAGO-induced inhibitory responses were not affected following blockade of L-type calcium channels by nifedipine. These findings indicate that μ-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, μ-opioid sensitive neurons were also suppressed by muscarinic receptor activation, while smaller, μ-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 μ-opioid receptor activation. These results suggest that μ-opioid regulation of calcium current may be an important functional mechanism in regulating neuronal excitability and synaptic transmission in the basal forebrain.