The mechanism of the actions of oxaliplatin on ion currents and action potentials in differentiated NG108-15 neuronal cells

Sheng-Nan Wu, Bing Shuo Chen, Yung Han Wu, Hsung Peng, Li Tzong Chen

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31 Citations (Scopus)

Abstract

Oxaliplatin (OXAL) is a platinum-based chemotherapeutic agent which is effective against advanced or metastatic gastrointestinal cancer. However, the mechanisms responsible for the development of the neuropathy induced by this agent remain unclear. In this study, we attempted to evaluate the possible effects of OXAL on ion currents and action potentials (APs) in NG108-15 cells differentiated with dibutyryl cyclic-AMP. Application of OXAL decreased the peak amplitude of voltage-gated Na+ current (INa) with no change in the overall current-voltage relations of the currents. This agent also produced a concentration-dependent slowing of INa inactivation. A further application of ranolazine reversed OXAL-induced slowing of INa inactivation. Unlike ranolazine or riluzole, OXAL had no effect on persistent INa elicited by long ramp pulses. OXAL (100 μM) also had little or no effect on the peak amplitude of L-type Ca2+ currents in NG108-15 cells, while it suppressed delayed-rectifier K+ current. In current-clamp recordings, OXAL alone reduced the amplitude of APs; however, it did not alter the duration of APs. However, after application of tefluthrin, OXAL did increase the duration of APs. Moreover, OXAL decreased the peak amplitude of INa with a concomitant reduction of current inactivation in HEK293T cells expressing SCN5A. The effects of OXAL on ion currents presented here may contribute to its neurotoxic actions in vivo.

Original languageEnglish
Pages (from-to)677-685
Number of pages9
JournalNeuroToxicology
Volume30
Issue number4
DOIs
Publication statusPublished - 2009 Jul 1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Toxicology

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