mu-Opioid receptor inhibits N-type Ca2+ channels in the calyx presynaptic terminal of the embryonic chick ciliary ganglion.
A study was made on the mechanisms by which enkephalins inhibit synaptic transmission at calyx-type presynaptic terminals in the ciliary ganglion of chick embryos at stages 39-40. Excitatory postsynaptic currents (EPSCs) were recorded by nystatin-perforated patch clamp at low [Ca2+]o and high [Mg2+]o. [Leu5]enkephalin (L-ENK, 1-10 microM) reduced the quantal content (m) without changing the quantal size (q). This effect was antagonized by naloxone (1 microM). Similar results were observed under conventional whole-cell clamp of the postsynaptic neuron. A specific agonist of the mu-opioid receptor, [D-Ala2, M-Me-Phe4,Gly5]enkephalin-ol (DAMGO) reduced m without changing q. A specific agonist of the delta-opioid receptor, [d-Pen2, d-Pen5]enkephalin (DPDPE) also reduced m without changing q. Both L-ENK and [Met5]enkephalin (M-ENK) reduced the stimulus-dependent increment of the intraterminal Ca2+ concentration (Delta[Ca2+]t) without affecting the decay time constant of the intraterminal Ca2+ concentration and basal Ca2+ level. This effect was antagonized by naloxone. DAMGO reduced Delta[Ca2+]t more effectively than DPDPE. When extracellular Ca2+ was replaced by Ba2+, the stimulus-dependent increment of the intraterminal Ba2+ concentration (Delta[Ba2+]t) was also reduced by L-ENK or DAMGO. L-ENK reduced Delta[Ca2+]t even in the presence of 4-aminopyridine (4-AP), which blocks the transient K+ conductance during the falling phase of the presynaptic action potential. When N-type Ca2+ channels were blocked by omega-conotoxin GVIA (omega-CgTxGVIA), the Delta[Ca2+]t was no longer sensitive to L-ENK and DAMGO. It is suggested that enkephalins reduce the transmitter release through presynaptic opioid receptors. The mu-opioid receptor may suppress presynaptic Ca2+ influx by selectively inhibiting N-type Ca2+ channels.
Endo
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Department of Physiology, Kyoto University Faculty of Medicine, Kyoto 606-8501 and Department of Neurophysiology, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Yawo
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H
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002642:Chick Embryo; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005726:Ganglia, Parasympathetic / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000737:chemistry / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001464:Barium; D009270:Naloxone; D004743:Enkephalin, Leucine; D020881:Enkephalin, D-Penicillamine (2,5)-; D020866:omega-Conotoxin GVIA; D002118:Calcium