Opioids hyperpolarize beta-endorphin neurons via mu-receptor activation of a potassium conductance.
Intracellular recordings were made from hypothalamic arcuate (ARC) neurons with biocytin-filled electrodes under current- and voltage-clamp in slices prepared from ovariectomized guinea pigs which were pretreated with estradiol. Forty-three neurons were identified after linking the intracellular biocytin with streptavidin-FITC and subsequently were examined for beta-endorphin immunoreactivity. Ten of these neurons were immunoreactive for beta-endorphin. beta-Endorphin neurons displayed the following passive membrane properties: RMP:-56 +/- 2 mV; Rin: 439 +/- 66 M omega; tau: 17.5 +/- 2.4 ms; and often fired spontaneously (5.9 +/- 2.2 Hz). These membrane characteristics were not different from identified neurons in the ARC that were not immunoreactive for beta-endorphin. beta-Endorphin neurons exhibited instantaneous inward rectification and time-dependent rectification. The mu-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO) decreased spontaneous firing, induced membrane hyperpolarization (12 +/- 2 mV; range 6-22 mV) and decreased the Rin (38 +/- 4%) of the beta-endorphin neurons. These effects of DAGO were blocked by the opioid antagonist naloxone (1 microM) and were not blocked by 1 microM TTX. DAGO-responsive cells were unaffected by either kappa- or delta-receptor opioid agonists. These results indicate that mu-receptors may be autoreceptors on ARC beta-endorphin neurons and that activation of opioid mu-receptors hyperpolarizes beta-endorphin neurons via an increase in K+ conductance. Therefore, opioid peptides may modulate opioid tone through an 'ultra-short loop' feedback control mechanism.
Kelly
M J
MJ
Department of Physiology, Oregon Health Sciences University, Portland.
Loose
M D
MD
Ronnekleiv
O K
OK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001426:Bacterial Proteins; D002462:Cell Membrane / Q000502:physiology; D004723:Endorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D008239:Lysine / Q000031:analogs & derivatives; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu; D019809:Streptavidin; D013861:Thiocyanates; D001615:beta-Endorphin / Q000378:metabolism*
D001426:Bacterial Proteins; D004723:Endorphins; D004745:Enkephalins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D015221:Potassium Channels; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D013861:Thiocyanates; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D001615:beta-Endorphin; D019809:Streptavidin; C013411:biocytin; D016650:Fluorescein-5-isothiocyanate; D008239:Lysine