Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons

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Abstract
1 The actions of the neuropeptide nociceptin on the calcium channel currents (IBa) of acutely dissociated rat periaqueductal grey (PAG) neurons were examined using whole-cell patch clamp techniques. These effects were compared with those of opioid receptor agonists and the GABAB receptor agonist baclofen. 2 Neurons from young adult rats (23 to 56 days old) expressed predominantly ω-conotoxin GVIA (N-type)- and ω-agatoxin IVA (P/Q-type)-sensitive IBa, together with smaller amounts of nimodipine-sensitive current and current resistant to all three blockers. There was proportionately more N-type IBa 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 μm) inhibited IBa in all PAG neurons, while the opioid agonist methionine enkephalin (met-enkephalin; 300 nm-10 μm) inhibited IBa in 40 % of neurons. The effects of met-enkephalin were reversed by the μ-opioid antagonist CTAP, and mimicked by the μ-opioid agonist DAMGO (300 nm-3 μm). The δ-opioid agonists DPDPE and deltorphin II, and the κ-opioid agonist U69593, did not affect IBa in any neuron. The actions of nociceptin were not mimicked or blocked by the opioid antagonist naloxone or the nociceptin analogue [desPhe1]-nociceptin. 4 The effects of nociceptin and baclofen on IBa were blocked by pretreatment of the neurons with pertussis toxin (500 ng ml−1, 8 h). 5 Nociceptin predominantly inhibited the N-type (EC50, 2 nm; maximum inhibition, 50 %) and P/Q-type (EC50, 7 nm; maximum inhibition, 33 %) IBa while having little effect on the L-type and R-type IBa. 6 These results are consistent with the previously described actions of nociceptin, baclofen and μ-opioids in PAG slices, whereby they couple to increases in an inwardly rectifying K+ conductance. These agonists thus have the potential to modulate the function of PAG neurons via a number of different cellular effectors.