Distinct populations of spinal cord lamina II interneurons expressing G-protein-gated potassium channels.
Noxious stimuli are sensed and carried to the spinal cord dorsal horn by A delta and C primary afferent fibers. Some of this input is relayed directly to supraspinal sites by projection neurons, whereas much of the input impinges on a heterogeneous population of interneurons in lamina II. Previously, we demonstrated that G-protein-gated inwardly rectifying potassium (GIRK) channels are expressed in lamina II of the mouse spinal cord and that pharmacologic ablation of spinal GIRK channels selectively blunts the analgesic effect of high but not lower doses of intrathecal mu-opioid receptor (MOR) agonists. Here, we report that GIRK channels formed by GIRK1 and GIRK2 subunits are found in two large populations of lamina II excitatory interneurons. One population displays relatively large apparent whole-cell capacitances and prominent GIRK-dependent current responses to the MOR agonist [D-Ala2,N-MePhe4,Gly-ol5] -enkephalin (DAMGO). A second population shows smaller apparent capacitance values and a GIRK-dependent response to the GABA(B) receptor agonist baclofen, but not DAMGO. Ultrastructural analysis revealed that GIRK subunits preferentially label type I synaptic glomeruli, suggesting that GIRK-containing lamina II interneurons receive prominent input from C fibers, while receiving little input from A delta fibers. Thus, excitatory interneurons in lamina II of the mouse spinal cord can be subdivided into different populations based on the neurotransmitter system coupled to GIRK channels. This important distinction will afford a unique opportunity to characterize spinal nociceptive circuitry with defined physiological significance.
Marker
Cheryl L
CL
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Luján
Rafael
R
Colón
José
J
Wickman
Kevin
K
D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000145:classification / Q000172:deficiency / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018079:Receptors, GABA / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
D000701:Analgesics, Opioid; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C107353:CGP 54626; D001418:Baclofen