title: Inward-rectifying K+(Kir2) leak conductance dampens the excitability of lamina I projection neurons in the neonatal rat.
abstract: Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life. To begin identifying these key leak conductances, the present study investigated the role of classical inward-rectifying K+(Kir2) channels in the regulation of intrinsic excitability in neonatal rat spino-PB and spino-PAG neurons. The data demonstrate that a reduction in Kir2-mediated conductance by external BaCl2significantly enhanced intrinsic membrane excitability in both groups. Similar results were observed in spino-PB neurons following Kir2 channel block with the selective antagonist ML133. In addition, voltage-clamp experiments showed that spino-PB and spino-PAG neurons express similar amounts of Kir2 current during the early postnatal period, suggesting that the differences in the prevalence of spontaneous activity between the two populations are not explained by differential expression of Kir2 channels. Overall, the results indicate that Kir2-mediated conductance tonically dampens the firing of multiple subpopulations of lamina I projection neurons during early life. Therefore, Kir2 channels are positioned to tightly shape the output of the immature spinal nociceptive circuit and thus regulate the ascending flow of nociceptive information to the developing brain, which has important functional implications for pediatric pain.
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Ford
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. Electronic address: mark.baccei@uc.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Baccei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D005260:Female; D008159:Lumbar Vertebrae; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000473:pathology; D065823:Parabrachial Nucleus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D002413:Cations, Divalent; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium
keywords: intrinsic excitability; leak conductance; projection neuron; superficial dorsal horn