Oxaliplatin, an anticancer agent that affects both Na+ and K+ channels in frog peripheral myelinated axons. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue General Physiology and Biophysics Année : 2006

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

Résumé

The use of oxaliplatin, a relatively new chemotherapeutic agent, is somewhat limited since it produces a specific peripheral neuropathy regarding other neurotoxic anticancer platinum analogues. In order to investigate the mechanism of such a peripheral neuropathy, the effects of 1-100 micromol/l oxaliplatin were assessed on the nodal ionic currents of single frog myelinated axons as a model of peripheral excitable membranes. Oxaliplatin decreased both Na(+) and K(+) currents in a dose-dependent manner and within 5-10 min, without producing any marked changes in the current kinetics. It was about three to eight times more effective in reducing the Na(+) than the K(+) current. In addition, it shifted the voltage-dependence of both Na(+) and K(+) conductances towards negative membrane potentials. A negative shift in the steady-state inactivation-voltage curve of the peak Na(+) current was also observed in the presence of oxaliplatin. These effects were not reversed by washing the myelinated axons with an oxaliplatin-free solution for at least 30 min. It is concluded that oxaliplatin modifies the voltage-dependent ionic channels mainly by altering the external surface membrane potential. The knowledge of such a mechanism may help to counteract the neurotoxic action of this anticancer agent.

Domaines

Neurobiologie
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Dates et versions

hal-00109506 , version 1 (24-10-2006)

Identifiants

  • HAL Id : hal-00109506 , version 1
  • PUBMED : 17197725

Citer

Evelyne Benoit, S. Brienza, Jean-Marc Dubois. Oxaliplatin, an anticancer agent that affects both Na+ and K+ channels in frog peripheral myelinated axons.. General Physiology and Biophysics, 2006, 25 (3), pp.263-276. ⟨hal-00109506⟩

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