MODULATION OF CA2+ CHANNEL CURRENTS OF ACUTELY DISSOCIATED RAT PERIAQUEDUCTAL GREY NEURONS

1. The actions of the neuropeptide nociceptin on the calcium channel c urrents (I-Ba) of acutely dissociated rat periaqueductal grey (PAG) ne urons were examined using whole-cell patch clamp techniques. These eff ects were compared with those of opioid receptor agonists and the GABA (B) receptor agonist baclofen. 2. Neurons from young adult rats (23 to 58 days old) expressed predominantly omega-conotoxin GVIA (N-type)- a nd omega-agatoxin IVA (P/Q-type)-sensitive I-Ba, together with smaller amounts of nimodipine-sensitive current and current resistant to all three blockers. There was proportionately more N-type I-Ba in neurons from female rats and proportionately more resistant current in neurons from male rats. 3. Nociceptin (EC50, 5 nM) and baclofen (EC50, 0.8 mu M) inhibited I-Ba in all PAG neurons, while the opioid agonist methio nine enkephalin (met-enkephalin; 300 nM-10 mu M) inhibited I-Ba in 40% of neurons. The effects of met-enkephalin were reversed by the mu-opi oid antagonist CTAP, and mimicked by the mu-opioid agonist DAMGO (300 nM-3 mu M). The S-opioid agonists DPDPE and deltorphin II, and the Ic- opioid agonist U69593, did not affect I-Ba in any neuron. The actions of nociceptin were not mimicked or blocked by the opioid antagonist na loxone or the nociceptin analogue [desPhe(1)]-nociceptin. 4. The effec ts of nociceptin and baclofen on I-Ba were blocked by pretreatment of the neurons with pertussis toxin (500 ng ml(-1) 8 h). 5. Nociceptin pr edominantly inhibited the N-type (EC50, 2 nM; maximum inhibition, 50%) and P/Q-type (EC50, 7 nM; maximum inhibition, 33 %) I-Ba while having little effect on the L-type and R-type I-Ba. 6. These results are con sistent with the previously described actions of nociceptin, baclofen and mu-opioids in FAG slices, whereby they couple to increases in an i nwardly rectifying K+ conductance. These agonists thus have the potent ial to modulate the function of FAG neurons via a number of different cellular effecters.