Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro.
Presynaptic modulation of synaptic transmission in rat subthalamic nucleus (STN) neurons was investigated using whole-cell patch-clamp recordings in brain slices. Evoked GABAergic inhibitory postsynaptic currents (IPSCs) were reversibly reduced by methionine enkephalin (ME) with an IC(50) value of 1.1 +/- 0.3 microM. The action of ME was mimicked by the mu-selective agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO), and was partially blocked by the mu-selective antagonists naloxonazine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP). Evoked GABA(A) IPSCs were also inhibited by the delta-selective agonist [D-Pen(2,5)]-enkephalin (DPDPE), but not by the kappa-selective agonist (+)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) and the orphan receptor agonist orphanin FQ/nociceptin (OFQ). DPDPE-induced inhibition was completely blocked by the delta-selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). ME, DAMGO and DPDPE increased the paired-pulse ratio of IPSCs. Evoked excitatory postsynaptic currents (EPSCs) were reversibly reduced by ME with an IC(50) value of 0.35 +/- 0.14 microM. Inhibition by ME was associated with an increase in the paired-pulse ratio of EPSCs. The action of ME was mimicked by DAMGO, and blocked by naloxonazine. DPDPE had little effect on evoked EPSCs. Neither U-69593 nor OFQ had any effect. ME significantly decreased the frequency of spontaneous miniature EPSCs (mEPSCs) without change in their amplitude. The action of ME was mimicked by DAMGO. DPDPE had no effect. The presynaptic voltage-dependent potassium conductance blocker 4-aminopyridine (4-AP, 100 microM) abolished the inhibitory effects of ME on evoked IPSCs and EPSCs. In contrast, 4-AP only partially blocked the actions of baclofen. These results suggest that opioids inhibit inhibitory synaptic transmission in the STN through the activation of presynaptic mu- and delta- receptors. In contrast, inhibition of excitatory synaptic inputs to the STN occurs through the activation of only mu-receptors. Both inhibitions may be mediated by blockade of voltage-dependent potassium conductance.
Shen
Ke-Zhong
KZ
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, USA.
Johnson
Steven W
SW
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009292:Narcotic Antagonists; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors; D020531:Subthalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D009292:Narcotic Antagonists; D015221:Potassium Channels; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D017661:Receptors, Presynaptic; D017480:Receptors, sigma; D005680:gamma-Aminobutyric Acid