Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 1, pp 47–59

Proliferation of human lens epithelial cells (HLE-B3) is inhibited by blocking of voltage-gated calcium channels

Cell and Molecular Physiology

Abstract

Calcium, as an integral part of a large number of cellular regulatory pathways, is selective in the control of specific cell functions like the start of G1 phase in cell cycle. Cell proliferation has been suggested to depend on increasing intracellular calcium levels. A major regulatory pathway for intracellular calcium is the calcium influx into the cell via voltage-gated calcium channels. T-type and L-type calcium channels are substantially present in human lens epithelial cell (hLEC), and total calcium currents are inhibited by mibefradil. Here, the hypothesis was tested if calcium influx via Cav channels regulates proliferation in epithelial cells. Cell proliferation was determined by cell culture assays using the L- and T-type Cav channel blockers mibefradil and verapamil as modulators for calcium influx. Calcium influx was investigated using the Manganese quench technique. Western blot experiments were accomplished under standard conditions using antibodies against MAPK 3. Mibefradil as well as verapamil impaired cell proliferation, but in different concentration ranges. Furthermore, the activation of MAPK 3 was reduced by both antagonists. Calcium influx was also reduced in the presence of both blockers. We conclude that the transmembrane influx of Ca2+ through Cav channels contributes to the regulation of hLEC proliferation, identifying Cav channel blockers as potential therapeutic substances in ocular diseases.

Keywords

Voltage-dependent calcium channel Ca2+ influx T-type calcium channel Protein phosphorylation Epithelial cell 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Institute of physiologyUniversity of RostockRostockGermany

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