title: Opioidergic modulation of voltage-activated K+ currents in magnocellular neurons of the supraoptic nucleus in rat.
abstract: 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 mu-receptor agonist D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO, 2 microM) affected K+ currents in 55% of magnocellular neurons recorded from. In these putative oxytocinergic cells, DAMGO increased the delayed rectifier current (IK(V)) amplitude by approximately 50% without significant effects on its activation kinetics. The transient A current (IA) was enhanced by DAMGO by approximately 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-kappa-opioid antagonist naloxone (10 microM). The kappa-opioid agonist trans-(+/-)-3, 4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide (U50,488; 10 microM) strongly suppressed IK(V) by approximately 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 IA by approximately 29% and tau of inactivation by -20% in DAMGO-sensitive cells. In contrast, in DAMGO-insensitive cells U50,488 increased IA by approximately 23% and strongly accelerated inactivation (tau -44%). The effects of U50,488 were suppressed by the selective kappa-receptor antagonist nor-binaltorphimine (5 microM). We conclude that mu- and kappa-opioidergic inputs decrease and increase excitability of oxytocinergic MCNs, respectively, through modulation of voltage-dependent K+ currents. In vasopressinergic MCNs, kappa-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.
authors: Institut für Physiologie der Charité, AG Molekulare Zellphysiologie, D-10117 Berlin, Germany.
authors: W
authors: W
authors: Müller
authors: S
authors: S
authors: Hallermann
authors: D
authors: D
authors: Swandulla
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D013495:Supraoptic Nucleus / Q000737:chemistry / Q000166:cytology* / Q000502:physiology
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer