Calcium channel blockers inhibit galvanotaxis in human keratinocytes

Donna R. Trollinger, Roslyn Rivkah Isseroff, Richard Nuccitelli

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Directed migration of keratinocytes is essential for wound healing. The migration of human keratinocytes in vitro is strongly influenced by the presence of a physiological electric field and these cells migrate towards the negative pole of such a field (galvanotaxis). We have previously shown that the depletion of extracellular calcium blocks the directional migration of cultured human keratinocytes in an electric field (Fang et al., 1998; J Invest Dermatol 111:751-756). Here we further investigate the role of calcium influx on the directionality and migration speed of keratinocytes during electric field exposure with the use of Ca2+ channel blockers. A constant, physiological electric field strength of 100 mV/mm was imposed on the cultured cells for 1 h. To determine the role of calcium influx during galvaotaxis we tested the effects of the voltage-dependent cation channel blockers, verapamil and amiloride, as well as the inorganic Ca2+ channel blockers, Ni2+ and Gd3+ and the Ca2+ substitute, Sr2+, on the speed and directionality of keratinocyte migration during galvanotaxis. Neither amiloride (10 μM) nor verapamil (10 μM) had any effect on the galvanotaxis response. Therefore, calcium influx through amiloride-sensitive channels is not required for galvanotaxis, and membrane depolarization via K+ channel activity is also not required. In contrast, Sr2+ (5 mM), Ni2+ (1-5 mM), and Gd3+ (100 μM) all significantly inhibit the directional migratory response to some degree. While Sr2+ strongly inhibits directed migration, the cells exhibit nearly normal migration speeds. These findings suggest that calcium influx through Ca2+ channels is required for directed migration of keratinocytes during galvanotaxis and that directional migration and migration speed are probably controlled by separate mechanisms.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Cellular Physiology
Volume193
Issue number1
DOIs
StatePublished - Oct 2002

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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