Opioidergic modulation of voltage-activated K+ currents in magnocellular neurons of the supraoptic nucleus in rat

Opioidergic modulation plays an important role in the control of oxytocin a nd vasopressin release by magnocellular neurons (MCNs) in the supraoptic an d paraventricular nuclei of the hypothalamus. We have used whole cell patch -clamp recording in acute slices of the supraoptic nucleus (SONT) of the hy pothalamus to study opioidergic modulation of voltage-dependent K+ currents in MCNs that are involved in release activity. The mu-receptor agonist D-A la(2), N-Me-Phe(4), Gly(5)-ol-enkephalin (DAMGO, 2 mu M) affected K+ curren ts in 55% of magnocellular neurons recorded from. In these putative oxytoci nergic cells, DAMGO increased the delayed rectifier current (I-K(V)) amplit ude by similar to 50% without significant effects on its activation kinetic s. The transient A current (I-A) was enhanced by DAMGO by similar to 36%. I ts inactivation kinetic was accelerated slightly while the Voltage dependen ce of steady-state inactivation was shifted by -6 mV to more negative poten tials. All DAMGO effects were blocked by the preferential non-kappa-opioid antagonist naloxone (10 mu M) The kappa-opioid agonist trans-(+/-)-3,4-dich loro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide (U50,488; 10 mu M) strongly suppressed I-K(V) by similar to 57% and evoked a 20-mV hyper polarizing shift and an acceleration of activation in both, DAMGO-sensitive and -insensitive putative vasopressinergic MCNs. U50,488 reduced I-A by si milar to 29% and tau of inactivation by -20% in DAMGO-sensitive cells. In c ontrast, in DAMGO-insensitive cells U50,488 increased I-A by similar to 23% and strongly accelerated inactivation (tau -44%). The effects of U50,488 w ere suppressed by the selective kappa-receptor antagonist nor-binaltorphimi ne (5 mu M). We conclude that mu- and kappa-opioidergic inputs decrease and increase excitability of oxytocinergic MCNs, respectively, through modulat ion of voltage dependent K+ currents. In vasopressinergic MCNs, kappa-opioi dergic inputs differentially modulate these K+ currents. The modulation of K+ currents is assumed to significantly contribute to opioidergic control o f hormone release by MCNs within the supraoptic nucleus and from the axon t erminals in the neural lobe.