Modulation of Ca super(2+) channel current by mu opioid receptors in prefrontal cortex pyramidal neurons in rats

Our work assesses the effects of mu opioid receptor activation on high-threshold Ca super(2+)/Ba super(2+) currents in freshly dispersed pyramidal neurons of the medial prefrontal cortex in rats. Application of the specific mu receptor agonist (D-Ala super(2), N-Me-Phe super(4), Gly super(5)-ol)-enkephalin (DAMGO) at 1 mu M decreased Ca super(2+) current amplitudes from 0.72 to 0.49 nA. The effect was abolished by naloxone and omega -Conotoxin GVIA. Inhibition was not abolished by strong depolarisation of the cell membrane. In addition, a macroscopic Ba super(2+) current recorded in cell-attached configuration was inhibited when DAMGO was applied outside the patch pipette. An adenylyl cyclase inhibitor (SQ 22536) and a protein kinase A inhibitor (H-89) decreased Ca super(2+) current amplitude. Moreover, the inhibitory effect of mu . opioid receptors on Ca super(2+) currents required the activation of protein kinase A. We conclude that activation of mu opioid receptors in medial prefrontal cortex pyramidal neurons inhibits N type Ca super(2+) channel currents, and that protein kinase A is involved in this transduction pathway.