Endothelin uncouples gap junctions in sustentacular cells and olfactory ensheathing cells of the olfactory mucosa

Eur J Neurosci. 2014 Sep;40(6):2878-87. doi: 10.1111/ejn.12665. Epub 2014 Jul 4.

Abstract

Several factors modulate the first step of odour detection in the rat olfactory mucosa (OM). Among others, vasoactive peptides such as endothelin might play multifaceted roles in the different OM cells. Like their counterparts in the central nervous system, the olfactory sensory neurons are encompassed by different glial-like non-neuronal OM cells; sustentacular cells (SCs) surround their cell bodies, whereas olfactory ensheathing cells (OECs) wrap their axons. Whereas SCs maintain both the structural and ionic integrity of the OM, OECs assure protection, local blood flow control and guiding of olfactory sensory neuron axons toward the olfactory bulb. We previously showed that these non-neuronal OM cells are particularly responsive to endothelin in vitro. Here, we confirmed that the endothelin system is strongly expressed in the OM using in situ hybridization. We then further explored the effects of endothelin on SCs and OECs using electrophysiological recordings and calcium imaging approaches on both in vitro and ex vivo OM preparations. Endothelin induced both robust calcium signals and gap junction uncoupling in both types of cells. This latter effect was mimicked by carbenoxolone, a known gap junction uncoupling agent. However, although endothelin is known for its antiapoptotic effect in the OM, the uncoupling of gap junctions by carbenoxolone was not sufficient to limit the cellular death induced by serum deprivation in OM primary culture. The functional consequence of the endothelin 1-induced reduction of the gap junctional communication between OM non-neuronal cells thus remains to be elucidated.

Keywords: calcium signals; glial cells; olfaction; olfactory mucosa; rat; slices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Carbenoxolone / pharmacology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cells, Cultured
  • Electric Stimulation
  • Endothelins / metabolism*
  • Gap Junctions / drug effects
  • Gap Junctions / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Neuroglia / drug effects
  • Neuroglia / physiology*
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / physiology*
  • Optical Imaging
  • Patch-Clamp Techniques
  • Rats, Wistar
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology*
  • Sensory System Agents / pharmacology
  • Tissue Culture Techniques

Substances

  • Endothelins
  • Sensory System Agents
  • L-Lactate Dehydrogenase
  • Carbenoxolone
  • Calcium