title: Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents Ih and ISK.
abstract: Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. Renshaw cells can be identified in vitro using anatomical and cellular criteria; however, their functional role in locomotion remains poorly defined because of the difficulty of functionally isolating Renshaw cells from surrounding motor circuits. Here we aimed to investigate whether the cholinergic nicotinic receptor alpha2 (Chrna2) can be used to identify Renshaw cells (RCs(α2)) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RCs(α2) properties confirmed that neurons genetically marked by the Chrna2-Cre mouse line together with a fluorescent reporter mouse line are Renshaw cells. Whole-cell patch-clamp recordings revealed that RCs(α2) constitute an electrophysiologically stereotyped population with a resting membrane potential of -50.5 ± 0.4 mV and an input resistance of 233.1 ± 11 MΩ. We identified a ZD7288-sensitive hyperpolarization-activated cation current (Ih) in all RCs(α2), contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RCs(α2) to express small calcium-activated potassium currents (I(SK)) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RCs(α2) can be genetically targeted through their selective Chrna2 expression and that they display currents known to modulate rebound excitation and firing frequency. The genetic identification of Renshaw cells and their electrophysiological profile is required for genetic and pharmacological manipulation as well as computational simulations with the aim to understand their functional role.
authors.affiliation: Department of Neuroscience, Uppsala University, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Sharn
authors.initials: S
authors.lastname: Perry
authors.forename: Henrik
authors.initials: H
authors.lastname: Gezelius
authors.forename: Martin
authors.initials: M
authors.lastname: Larhammar
authors.forename: Markus M
authors.initials: MM
authors.lastname: Hilscher
authors.forename: Boris
authors.initials: B
authors.lastname: Lamotte d'Incamps
authors.forename: Katarina E
authors.initials: KE
authors.lastname: Leao
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D008159:Lumbar Vertebrae; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D066293:Renshaw Cells / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013126:Spinal Nerve Roots / Q000502:physiology; D014018:Tissue Distribution
chemical_list: C000603869:CHRNA2 protein, mouse; D007473:Ion Channels; D018377:Neurotransmitter Agents; D011743:Pyrimidines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C082246:ICI D2788; D001030:Apamin
keywords: interneurons; mouse; nicotinic acetylcholine receptor alpha2; recurrent inhibition; spinal cord