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

Rok, strany: 2006, 263 - 276

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 µmol/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.

ISO 690:

Benoit, E., Brienza, S., Dubois, J. 2006. Oxaliplatin, an anticancer agent that affects both Na⁺ and K⁺ channels in frog peripheral myelinated axons. In General Physiology and Biophysics, vol. 25, no.3, pp. 263-276. 0231-5882.

APA:

Benoit, E., Brienza, S., Dubois, J. (2006). Oxaliplatin, an anticancer agent that affects both Na⁺ and K⁺ channels in frog peripheral myelinated axons. General Physiology and Biophysics, 25(3), 263-276. 0231-5882.