Opioids at low concentration decrease openings of K+ channels in sensory ganglion neurons.
Previous studies showed that low concentrations of opioids prolong the calcium-dependent component of the action potential duration (APD) of dorsal root ganglion (DRG) neurons, whereas higher concentrations shorten the APD. In the present study whole-cell voltage-clamp, as well as cell-attached membrane-patch voltage-clamp, recordings demonstrate that application of picomolar to nanomolar concentrations of mu, delta or kappa opioid agonists (DAGO, DPDPE or dynorphin) to DRG neurons in dissociated cell cultures reversibly decreased the activities of voltage-sensitive K+ channels. Pretreatment of DRG neurons with the opioid receptor antagonists, naloxone (30 nM) or diprenorphine (1 nM) prevented mu/delta or kappa opioid-induced decreases in K+ channel activities, respectively. Since opioids added to the bath solution decreased the activities of K+ channels in the membrane patch sealed off by the pipette tip, our results provide strong evidence that some modes of excitatory modulation of the action potential of DRG neurons are mediated by diffusible second messengers. The data are consonant with our previous studies indicating that opioids can elicit excitatory effects on sensory neurons via cholera toxin-sensitive Gs-linked excitatory opioid receptors coupled to cyclic AMP-dependent ionic channels.
Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461.
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D000200:Action Potentials; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism*; D009292:Narcotic Antagonists; D009294:Narcotics / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000378:metabolism*; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000502:physiology*
D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D015221:Potassium Channels; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004399:Dynorphins; D020881:Enkephalin, D-Penicillamine (2,5)-