title: Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life.
abstract: Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst firing and are distinguished by a lower "leak" membrane conductance compared with adjacent nonbursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (K(ir)) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and nonpacemakers indicate the presence of functionally distinct K(ir) currents in these two populations at room temperature. However, K(ir) currents in both groups showed high sensitivity to block by extracellular Ba²⁺ (IC₅₀ ~ 10 μm), which suggests the presence of "classical" K(ir) (K(ir)2.x) channels in the neonatal SDH. The reduced K(ir) conductance within pacemakers is unlikely to be explained by an absence of particular K(ir)2.x isoforms, as immunohistochemical analysis revealed the expression of K(ir)2.1, K(ir)2.2, and K(ir)2.3 within spontaneously bursting neurons. Importantly, Ba²⁺ application unmasked rhythmic burst firing in ∼42% of nonbursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst firing within lamina I was enhanced in the presence of high internal concentrations of free Mg²⁺, consistent with its documented ability to block K(ir) channels from the intracellular side. Collectively, the results indicate that K(ir) channels are key modulators of pacemaker activity in newborn central pain networks.
authors: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA.
authors: Jie
authors: J
authors: Li
authors: Meredith L
authors: ML
authors: Blankenship
authors: Mark L
authors: ML
authors: Baccei
mesh_terms: D000367:Age Factors; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D009924:Organ Culture Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*
chemical_list: C490968:Kcnj4 protein, rat; C489461:Kir2.1 channel; C489463:Kir2.2 channel; D024661:Potassium Channels, Inwardly Rectifying