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NKCC1 Phosphorylation Stimulates Neurite Growth of Injured Adult Sensory Neurons: NKCC1 and regenerative growth

Abstract : Peripheral nerve section promotes regenerative, elongated neuritic growth of adult sensory neurons. While the role of chloride homeostasis, through the regulation of ionotropic GABA receptors, in the growth status of immature neurons in the central nervous system begins to emerge, nothing is known of its role in the regenerative growth of injured adult neurons. To analyze the intracellular Cl- variation following a sciatic nerve section in vivo, gramicidin perforated-patch recordings were used to study muscimol-induced currents in mice dorsal root ganglion neurons isolated from control and axotomized neurons. We show that the reversal potential of muscimol-induced current, EGABA-A was shifted towards depolarized potentials in axotomized neurons. This was due to Cl- influx since removal of extracellular Cl- prevented this shift. Application of bumetanide, an inhibitor of NKCC1 cotransporter and EGABA-A recordings in sensory neurons from NKCC1-/- mice, identified NKCC1 as being responsible for the increase in intracellular Cl- in axotomized neurons. In addition, we demonstrate with a phospho-NKCC1 antibody that nerve injury induces an increase in the phosphorylated form of NKCC1 in dorsal root ganglia that could account for intracellular Cl- accumulation. Time-lapse recordings of the neuritic growth of axotomized neurons show a faster growth velocity in comparison with control. Both bumetanide, the intrathecal injection of NKCC1 siRNA and the use of NKCC1-/- mice demonstrated that NKCC1 is involved in determining the velocity of elongated growth of axotomized neurons. Our results clearly show that NKCC1-induced increase in intracellular chloride concentration is a major event accompanying peripheral nerve regeneration.
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https://www.hal.inserm.fr/inserm-00164013
Contributor : Christian Hamel <>
Submitted on : Tuesday, May 18, 2010 - 4:05:18 PM
Last modification on : Wednesday, September 16, 2020 - 10:43:36 AM
Long-term archiving on: : Thursday, September 16, 2010 - 12:14:27 PM

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  • HAL Id : inserm-00164013, version 1
  • PUBMED : 17581962

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Simon Pieraut, Valérie Laurent-Matha, Chamroeun Sar, Thomas Hubert, Ilana Méchaly, et al.. NKCC1 Phosphorylation Stimulates Neurite Growth of Injured Adult Sensory Neurons: NKCC1 and regenerative growth. Journal of Neuroscience, Society for Neuroscience, 2007, 27 (25), pp.6751-9. ⟨inserm-00164013⟩

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