K(+) current regulates calcium-activated chloride current-induced after depolarization in axotomized sensory neurons.

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 Ca(2+)-activated Cl(-) current in subsets of medium and large sensory neurons. In the peripheral nervous system, the Ca(2+)-activated Cl(-) current can promote after depolarization (ADP) and may therefore be involved in excitability. In this study, we set the conditions for Ca(2+)-activated Cl(-) current activation during the electrical activity of axotomized sensory neurons. We used the whole-cell patch-clamp technique and Ca(2+) fluorescence measurements to record electrical activity or ionic currents associated with intracellular Ca(2+) transients. An analysis of Ca(2+) fluorescence variation under Ca(2+)-activated Cl(-) current activation showed that the Ca(2+) sensitivity of the Ca(2+)-activated Cl(-) current did not allow activation upon one action potential (AP) but instead necessitated intracellular Ca(2+) 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 Ca(2+)-activated Cl(-) current was responsible for the ADP observed during K(+) current inhibition. Thus, the Ca(2+)-activated Cl(-) current-induced ADP in axotomized sensory neurons is regulated by K(+) current density.

• Authors: Cécile Hilaire, Brice Campo, Sylvain André, Jean Valmier, Frédérique Scamps
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 22 Issue 5 Pg. 1073-80 (Sep 2005) ISSN: 0953-816X [Print] France
• PMID: 16176348 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chloride Channels
• Potassium Channels
• Adenosine Diphosphate
• Potassium
• Calcium

Topics

• Action Potentials (physiology)
• Adenosine Diphosphate (pharmacology)
• Animals
• Axotomy (methods)
• Calcium (metabolism)
• Chloride Channels (physiology)
• Electric Stimulation (methods)
• Female
• Ganglia, Spinal (cytology)
• Mice
• Neural Inhibition (drug effects, physiology)
• Neurons, Afferent (physiology)
• Potassium (physiology)
• Potassium Channels (physiology)
• Time Factors