Oxidative stress induced by cumene hydroperoxide evokes changes in neuronal excitability of rat motor cortex neurons

Neuroscience. 2015 Mar 19;289:85-98. doi: 10.1016/j.neuroscience.2014.12.055. Epub 2015 Jan 12.

Abstract

Oxidative stress and the production of reactive oxygen radicals play a key role in neuronal cell damage. This paper describes an in vitro study that explores the neuronal responses to oxidative stress focusing on changes in neuronal excitability and functional membrane properties. This study was carried out in pyramidal cells of the motor cortex by applying whole-cell patch-clamp techniques on brain slices from young adult rats. Oxygen-derived free radical formation was induced by bath application of 10μM cumene hydroperoxide (CH) for 30min. CH produced marked changes in the electrophysiological properties of neurons (n=30). Resting membrane potential became progressively depolarized, as well as depolarization voltage, with no variations in voltage threshold. Membrane resistance showed a biphasic behavior, increasing after 5min of drug exposure and then it started to decrease, even under control values, after 15 and 30min. At the same time, changes in membrane resistance produced compensatory variations in the rheobase. The amplitude of the action potentials diminished and the duration increased progressively over time. Some of the neurons under study also lost their ability to discharge action potentials in a repetitive way. Most of the neurons, however, kept their repetitive discharge even though their maximum frequency and gain decreased. Furthermore, cancelation of the repetitive firing discharge took place at intensities that decreased with time of exposure to CH, which resulted in a narrower working range. We can conclude that oxidative stress compromises both neuronal excitability and the capability of generating action potentials, and so this type of neuronal functional failure could precede the neuronal death characteristics of many neurodegenerative diseases.

Keywords: amyotrophic lateral sclerosis; cumene hydroperoxide; lipid peroxidation; neuronal excitability; patch clamp; pyramidal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Benzene Derivatives / pharmacology*
  • Electric Impedance
  • Female
  • Free Radicals / pharmacology*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Motor Cortex / drug effects*
  • Motor Cortex / physiopathology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / physiology
  • Rats, Wistar
  • Time Factors
  • Tissue Culture Techniques

Substances

  • Benzene Derivatives
  • Free Radicals
  • cumene hydroperoxide