mu-Opioid receptor activation reduces multiple components of high-threshold calcium current in rat sensory neurons.
Whole-cell patch-clamp recordings were used to characterize calcium channel types that are modulated by mu-opioid receptor activation in rat dorsal root ganglion (DRG) neurons. Five distinct components of high-threshold calcium current were isolated on the basis of their sensitivity to the selective channel blockers omega-conotoxin GVIA, nifedipine, omega-conotoxin MVIIC, or omega-agatoxin IVA. The mu-opioid selective agonist Tyr-Pro-NMePhe-D-Pro-NH2 (PLO17) routinely suppressed high-threshold currents and this effect was always reduced by omega-conotoxin GVIA. A fraction of PLO17-sensitive current remained after omega-conotoxin GVIA that was eliminated by application of omega-agatoxin IVA alone or in combination with omega-conotoxin MVIIC. Nifedipine had no effect on mu-opioid responses nor did PLO17 affect the slow component of tail current induced by Bay K 8644. These data suggest that mu-opioid receptors are negatively coupled to three types of calcium channels in rat DRG neurons, including an omega-conotoxin GVIA-sensitive (N-type) channel, an omega-agatoxin IVA-sensitive (P-type) channel and an omega-conotoxin MVIIC-sensitive, nifedipine/GVIA/omega-Aga IVA-resistant (presumptive Q-type) channel.
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Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008978:Mollusk Venoms / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D004723:Endorphins; D008978:Mollusk Venoms; D010455:Peptides; D017450:Receptors, Opioid, mu; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C044708:morphiceptin, N-Me-Phe(3)-; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D002118:Calcium