Single potassium channels opened by opioids in rat locus ceruleus neurons.
Currents through single-ion channels were recorded in the cell-attached configuration from locus ceruleus neurons enzymatically dissociated from newborn rats. When the selective mu opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol was in the patch-clamp electrode, unitary inward currents were observed with conductance of approximately 45 pS (measured at zero pipette potential, with 150 mM potassium in the recording electrode). Long silences, lasting many seconds to minutes, separated periods of activity of similar durations. Within such activity periods the distribution of closed times of the channels was best fitted by the sum of two exponential functions (time constants approximately 1 and 30 ms), and the durations of channel openings were fit by a single exponential function; mean open time increased from 2 to 120 ms as agonist concentration increased. Channel activity was not seen when high concentrations of opioids were applied to the neuron outside the patch-clamp recording electrode, indicating intimate coupling between receptor and potassium channel. Unitary currents with similar properties were also seen when pipettes contained alpha 2 adrenoceptor agonists or somatostatin. Taken with previous findings, the results indicate that mu opioid receptors, alpha 2 adrenoceptors, and somatostatin receptors can couple directly to membrane potassium channels through the local intermediary action of a GTP binding protein.
Miyake
M
M
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Christie
M J
MJ
North
R A
RA
D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists; D000818:Animals; D000831:Animals, Newborn; D000068438:Brimonidine Tartrate; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004553:Electric Conductivity; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology; D017450:Receptors, Opioid, mu; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D004723:Endorphins; D015221:Potassium Channels; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D017481:Receptors, Somatostatin; D009270:Naloxone; D000068438:Brimonidine Tartrate; D013004:Somatostatin; D004744:Enkephalin, Methionine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin