Pflügers Archiv - European Journal of Physiology

, Volume 464, Issue 3, pp 273–285 | Cite as

Melatonin down-regulates volume-sensitive chloride channels in fibroblasts

  • Ismail Ben Soussia
  • Frédérique Mies
  • Robert Naeije
  • Vadim Shlyonsky
Ion channels, Receptors and Transporters

Abstract

Melatonin has been reported to present with vasorelaxant and anti-fibrotic properties. We hypothesized that melatonin may down-regulate volume-regulated anion channels (VRAC) in fibroblasts to limit their migration and proliferation. While acute exposure of L929 fibroblasts to melatonin did not result in a significant decrease in VRAC current, pretreatment with 100 μM melatonin for 1 h decreased swelling-dependent activation of anion currents by 83 % as measured by whole-cell perforated patch-clamp technique. This down-regulation of VRAC currents was dose-dependent with a half-maximal inhibition of 3.02 ± 0.48 μM. Overnight treatment of cells with 100 nM melatonin had the same inhibitory potency as a 1-h treatment with 100 μM. A similar down-regulatory effect of melatonin on VRAC was observed in primary rat lung fibroblasts. The effect of melatonin was prevented by luzindole and K185 that suggests implication of MT2 receptor. GF109203X, a protein kinase C inhibitor, blocked melatonin’s action on VRAC, indicating that MT2 receptor activation results in stimulation of PKC. Consequently, melatonin inhibited regulatory volume decrease following hypotonic swelling of cells. Melatonin also decreased the migration of L929 fibroblasts through the same pathways that blocked VRAC. There was no significant inhibition of cell proliferation. Our study suggests that the attenuation of fibrosis and vascular remodeling by melatonin seen in animal models of hypertension and pulmonary fibrosis might be, in part, related to blunted fibroblast migration possibly through protein kinase C-mediated decrease in chloride channel activity.

Keywords

Patch-clamp Anion channel Melatonin receptor Cell volume Cell migration Cell proliferation 

Notes

Acknowledgments

This study was supported by funds from the Funds National pour la Recherche Scientifique (to R.N.) and the Funds d’Encouragement à la Recherche of Université Libre de Bruxelles (to V.S.). We would like to express our gratitude to Sarah Sariban-Sohraby for invaluable comments on the manuscript.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ismail Ben Soussia
    • 1
  • Frédérique Mies
    • 1
  • Robert Naeije
    • 1
  • Vadim Shlyonsky
    • 1
  1. 1.Department of PhysiologyUniversité Libre de BruxellesBrusselsBelgium

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