K+ current regulates calcium-activated chloride current-induced afterdepolarization in axotomized sensory neurons

Authors

  • Cécile Hilaire,

    1. 1 INSERM U 583, Hôpital St Eloi, 34295 Montpellier, France
      2 EA 481, Université Besançon, Place Leclerc, 25030, Besançon, France
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  • 2 Brice Campo,

    1. 1 INSERM U 583, Hôpital St Eloi, 34295 Montpellier, France
      2 EA 481, Université Besançon, Place Leclerc, 25030, Besançon, France
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    • *

      Present address: Addex Pharmaceuticals, 1228 Plan-les-Ouates, Geneva, Switzerland.

  • 1, Sylvain André,

    1. 1 INSERM U 583, Hôpital St Eloi, 34295 Montpellier, France
      2 EA 481, Université Besançon, Place Leclerc, 25030, Besançon, France
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  • 1 Jean Valmier,

    1. 1 INSERM U 583, Hôpital St Eloi, 34295 Montpellier, France
      2 EA 481, Université Besançon, Place Leclerc, 25030, Besançon, France
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  • and 1 Frédérique Scamps 1

    1. 1 INSERM U 583, Hôpital St Eloi, 34295 Montpellier, France
      2 EA 481, Université Besançon, Place Leclerc, 25030, Besançon, France
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Dr F. Scamps, Inserm U 583-INM, 80, rue Augustin FLICHE, BP 74103, 34091 Montpellier Cedex 5, France.
E-mail: scamps@univ-montp2.fr

Abstract

One of the major electrophysiological effects of axotomy is a hyperexcitability of injured afferents that is thought to be involved in peripheral neuropathic pain. The molecular determinants of injured sensory neuron excitability are complex and not all have been identified. We have previously shown that sciatic nerve section upregulates the Ca2+-activated Cl current in subsets of medium and large sensory neurons. In the peripheral nervous system, the Ca2+-activated Cl current can promote afterdepolarization (ADP) and may therefore be involved in excitability. In this study, we set the conditions for Ca2+-activated Cl current activation during the electrical activity of axotomized sensory neurons. We used the whole-cell patch-clamp technique and Ca2+ fluorescence measurements to record electrical activity or ionic currents associated with intracellular Ca2+ transients. An analysis of Ca2+ fluorescence variation under Ca2+-activated Cl current activation showed that the Ca2+ sensitivity of the Ca2+-activated Cl current did not allow activation upon one action potential (AP) but instead necessitated intracellular Ca2+ loading under high-frequency electrical activity or AP lengthening. Nevertheless, ADP was exclusively recorded under AP lengthening following K+ current inhibition with either extracellular tetraethylammonium or intracellular Cs+. The measurement of APs and ionic currents associated with the use of niflumic acid to inhibit Cl currents showed that the Ca2+-activated Cl current was responsible for the ADP observed during K+ current inhibition. Thus, the Ca2+-activated Cl current-induced ADP in axotomized sensory neurons is regulated by K+ current density.

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