TY - JOUR
T1 - Actions of the ORL1 receptor ligand nociceptin on membrane properties of rat periaqueductal gray neurons in vitro
AU - Vaughan, Christopher W.
AU - Ingram, Susan L.
AU - Christie, MacDonald J.
PY - 1997
Y1 - 1997
N2 - The actions of the endogenous ORL1-receptor ligand nociceptin on the membrane properties and synaptic currents in rat periaqueductal gray (PAG) neurons were examined by the use of whole-cell patch-clamp recording in brain slices. Nociceptin produced an outward current in all neurons tested, with an EC50 of 39 ± 7 nM. The outward current was unaffected by naloxone. Outward currents reversed polarity at 110 ± 3 mV in 2.5 mM extracellular potassium, and the reversal potential increased when the extracellular potassium concentration was raised (slope = 66.3 mV/log[K+](o) mM). Thus, the nociceptin-induced outward current was attributable to an increased K+ conductance. Nociceptin inhibited evoked fast GABAergic (IPSCs) and glutamatergic (EPSCs) postsynaptic currents and increased paired-pulse facilitation in a subpopulation of PAG neurons. Nociceptin inhibited evoked IPSCs and EPSCs in ~50% of neurons throughout the PAG, except in the ventrolateral PAG, where nociceptin inhibited evoked IPSCs in most neurons. Nociceptin decreased the frequency of spontaneous miniature postsynaptic currents (mIPSCs and mEPSCs) in a subpopulation of PAG neurons but had no effect on their amplitude distributions. Thus, nociceptin had a presynaptic inhibitory effect on transmitter release. These findings suggest that nociceptin, via its pre- and postsynaptic actions, has the potential to modulate the analgesic, behavioral, and autonomic functions of the PAG.
AB - The actions of the endogenous ORL1-receptor ligand nociceptin on the membrane properties and synaptic currents in rat periaqueductal gray (PAG) neurons were examined by the use of whole-cell patch-clamp recording in brain slices. Nociceptin produced an outward current in all neurons tested, with an EC50 of 39 ± 7 nM. The outward current was unaffected by naloxone. Outward currents reversed polarity at 110 ± 3 mV in 2.5 mM extracellular potassium, and the reversal potential increased when the extracellular potassium concentration was raised (slope = 66.3 mV/log[K+](o) mM). Thus, the nociceptin-induced outward current was attributable to an increased K+ conductance. Nociceptin inhibited evoked fast GABAergic (IPSCs) and glutamatergic (EPSCs) postsynaptic currents and increased paired-pulse facilitation in a subpopulation of PAG neurons. Nociceptin inhibited evoked IPSCs and EPSCs in ~50% of neurons throughout the PAG, except in the ventrolateral PAG, where nociceptin inhibited evoked IPSCs in most neurons. Nociceptin decreased the frequency of spontaneous miniature postsynaptic currents (mIPSCs and mEPSCs) in a subpopulation of PAG neurons but had no effect on their amplitude distributions. Thus, nociceptin had a presynaptic inhibitory effect on transmitter release. These findings suggest that nociceptin, via its pre- and postsynaptic actions, has the potential to modulate the analgesic, behavioral, and autonomic functions of the PAG.
KW - ORL receptor
KW - analgesia
KW - nociceptin
KW - opioid receptor
KW - orphan receptor
KW - periaqueductal gray
KW - potassium channel
KW - presynaptic inhibition
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UR - http://www.scopus.com/inward/citedby.url?scp=0030614373&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.17-03-00996.1997
DO - 10.1523/jneurosci.17-03-00996.1997
M3 - Article
C2 - 8994054
AN - SCOPUS:0030614373
SN - 0270-6474
VL - 17
SP - 996
EP - 1003
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 3
ER -