Agonists at mu-opioid, M2-muscarinic and GABAB-receptors increase the same potassium conductance in rat lateral parabrachial neurones.
1. Intracellular recordings of membrane potential and current were made from neurones in the lateral parabrachial nucleus in slices of rat brain in vitro. 2. The membrane was hyperpolarized by the opioid peptides Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL, 0.01-1 microM) and [Met5]enkephalin (3-30 microM), though not by Tyr-D-Pen-Gly-Phe-D-Pen and U50488. In two experiments, naloxone competitively antagonized the effects of DAGOL and [Met]enkephalin with equilibrium dissociation constants of 0.8 and 3.2 nM, respectively. 3. Baclofen (0.3-30 microM) also hyperpolarized the neurones; this action was unaffected by naloxone. 4. DAGOL, [Met5]enkephalin and baclofen caused outward currents at the resting potential. These currents reversed polarity at a membrane potential which changed with the logarithm of the extracellular potassium concentration. 5. Muscarine has been shown previously to increase the potassium conductance by an action at M2-receptors: the potassium currents induced by maximal concentrations of muscarine, baclofen and [Met5]enkephalin were non-additive, indicating that these agonists opened the same population of potassium channels. 6. Noradrenaline, UK14304, carboxamidotryptamine, dopamine, adenosine and somatostatin had little or no effect on membrane potential. 7. It is concluded that rat lateral parabrachial neurones express mu-opioid, gamma-aminobutyric acidB (GABAB), and M2-muscarinic receptors: activation of any of these receptors increases the potassium conductance of the membrane and inhibits the neurones through hyperpolarization.
Christie
M J
MJ
Vollum Institute, Oregon Health Sciences University, Portland 97201.
North
R A
RA
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu
D004723:Endorphins; D015221:Potassium Channels; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009116:Muscarine; D001418:Baclofen