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Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
07:42

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Published on: April 26, 2012

Oxaliplatin, an anticancer agent that affects both Na+ and K+ channels in frog peripheral myelinated axons

E Benoit1, S Brienza, J M Dubois

  • 1Laboratoire de Neurobiologie Cellulaire et Moléculaire, UPR 9040, CNRS, bât. 32-33, 91198 Gif-sur-Yvette cedex, France. benoit@nbcm.cnrs-gif.fr

General Physiology and Biophysics
|January 2, 2007
PubMed

Insights

Oxaliplatin, a chemotherapy drug, causes peripheral neuropathy by altering nerve cell ion channels. This study reveals oxaliplatin affects sodium and potassium currents, potentially explaining its neurotoxic side effects.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cellular Electrophysiology

Background:

  • Oxaliplatin is a platinum-based chemotherapy agent.
  • Oxaliplatin use is limited by neurotoxicity, specifically peripheral neuropathy.
  • The precise mechanism of oxaliplatin-induced peripheral neuropathy is not fully understood.

Purpose of the Study:

  • To investigate the effects of oxaliplatin on the ionic currents of excitable membranes.
  • To elucidate the mechanism underlying oxaliplatin's peripheral neurotoxicity.

Main Methods:

  • Assessed the effects of oxaliplatin (1-100 micromol/l) on nodal ionic currents in single frog myelinated axons.
  • Used voltage-clamp techniques to measure sodium (Na+) and potassium (K+) currents.
  • Examined changes in current kinetics, voltage-dependence, and inactivation properties.

Main Results:

  • Oxaliplatin dose-dependently decreased both Na+ and K+ currents within 5-10 minutes.
  • Oxaliplatin was 3-8 times more potent in reducing Na+ current compared to K+ current.
  • Oxaliplatin shifted the voltage-dependence of Na+ and K+ conductances and Na+ current inactivation towards negative potentials.
  • Observed effects were irreversible upon washout.

Conclusions:

  • Oxaliplatin modifies voltage-dependent ionic channels, primarily by altering the external surface membrane potential.
  • These electrophysiological changes provide a mechanistic basis for oxaliplatin-induced peripheral neuropathy.
  • Understanding this mechanism may aid in developing strategies to counteract oxaliplatin's neurotoxic effects.

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