Altered excitability of cultured chromaffin cells following exposure to multi-walled carbon nanotubes

Abstract

We studied the effects of multi-walled carbon nanotubes (MWCNTs) on the electrophysiological properties of cultured mouse chromaffin cells, a model of spontaneously firing cells. The exposure of chromaffin cells to MWCNTs at increasing concentrations (30–263 μg/ml) for 24 h reduced, in a dose-dependent way, both the cell membrane input resistance and the number of spontaneously active cells (from 80–52%). Active cells that survived from the toxic effects of MWCNTs exhibited more positive resting potentials, higher firing frequencies and unaltered voltage-gated Ca²⁺, Na⁺ and K+ current amplitudes. MWCNTs slowed down the inactivation kinetics of Ca²⁺-dependent BK channels. These electrophysiological effects were accompanied by MWCNTs internalization, as confirmed by transmission electron microscopy, indicating that most of the toxic effects derive from a dose-dependent MWCNTs-cell interaction that damages the spontaneous cell activity.

Keywords::

• MWCNTs
• voltage-gated Na⁺ and K+ channels
• Ca²⁺ and BK channels
• adrenal chromaffin cells
• action potential firing
• input resistance

Acknowledgments

We thank Drs M. Colonna, C. Franchino and A. Renna for discussions and help during the experiments.

Declaration of interest: The work was supported by the Regione Piemonte [grant number D14-2005 to E.C. and CIPE 2006 Project “Nanoparticles: from their impact on the environment and human health to safer production and usage (NANOSAFE)” to B.F.], by the Compagnia San Paolo [grant to the NIS Center] and by the Italian Ministry of Education, University and Research (MIUR), Programmi di Ricerca scientifica di rilevante Interesse Nazionale (PRIN) 2007, prot. 2007FA34TE. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.