The Journal of Neurophysiology Vol. 81 No. 4 April 1999, pp. 1617-1625
Copyright ©1999 by the American Physiological Society

Opioidergic Modulation of Voltage-Activated K⁺ Currents in Magnocellular Neurons of the Supraoptic Nucleus in Rat

 ¹Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, D-91054 Erlangen; and  ²Institut für Physiologie der Charité, AG Molekulare Zellphysiologie, D-10117 Berlin, Germany

Müller, Wolfgang, Stephan Hallermann, and Dieter Swandulla. 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 and vasopressin release by magnocellular neurons (MCNs) in the supraoptic and paraventricular nuclei of the hypothalamus. We have used whole cell patch-clamp recording in acute slices of the supraoptic nucleus (SON) of the hypothalamus to study opioidergic modulation of voltage-dependent K⁺ currents in MCNs that are involved in release activity. The µ-receptor agonist D-Ala², N-Me-Phe⁴, Gly⁵-ol-enkephalin (DAMGO, 2 µM) affected K⁺ currents in 55% of magnocellular neurons recorded from. In these putative oxytocinergic cells, DAMGO increased the delayed rectifier current (I_K(V)) amplitude by ~50% without significant effects on its activation kinetics. The transient A current (I_A) was enhanced by DAMGO by ~36%. Its inactivation kinetic was accelerated slightly while the voltage dependence of steady-state inactivation was shifted by 6 mV to more negative potentials. All DAMGO effects were blocked by the preferential non--opioid antagonist naloxone (10 µM). The -opioid agonist trans-(±)-3,4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide (U50,488; 10 µM) strongly suppressed I_K(V) by ~57% and evoked a 20-mV hyperpolarizing shift and an acceleration of activation in both, DAMGO-sensitive and -insensitive putative vasopressinergic MCNs. U50,488 reduced I_A by ~29% and  of inactivation by 20% in DAMGO-sensitive cells. In contrast, in DAMGO-insensitive cells U50,488 increased I_A by ~23% and strongly accelerated inactivation ( 44%). The effects of U50,488 were suppressed by the selective -receptor antagonist nor-binaltorphimine (5 µM). We conclude that µ- and -opioidergic inputs decrease and increase excitability of oxytocinergic MCNs, respectively, through modulation of voltage-dependent K⁺ currents. In vasopressinergic MCNs, -opioidergic inputs differentially modulate these K⁺ currents. The modulation of K⁺ currents is assumed to significantly contribute to opioidergic control of hormone release by MCNs within the supraoptic nucleus and from the axon terminals in the neural lobe.