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Calcium channel blockers inhibit galvanotaxis in human keratinocytes
Author(s) -
Trollinger Donna R.,
Rivkah Isseroff R.,
Nuccitelli Richard
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10144
Subject(s) - amiloride , verapamil , depolarization , calcium channel , calcium , biophysics , channel blocker , voltage dependent calcium channel , chemistry , extracellular , electric field , biology , biochemistry , physics , sodium , organic chemistry , quantum mechanics
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 Ca 2+ 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 galvanotaxis we tested the effects of the voltage‐dependent cation channel blockers, verapamil and amiloride, as well as the inorganic Ca 2+ channel blockers, Ni 2+ and Gd 3+ and the Ca 2+ substitute, Sr 2+ , 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, Sr 2+ (5 mM), Ni 2+ (1–5 mM), and Gd 3+ (100 μM) all significantly inhibit the directional migratory response to some degree. While Sr 2+ strongly inhibits directed migration, the cells exhibit nearly normal migration speeds. These findings suggest that calcium influx through Ca 2+ channels is required for directed migration of keratinocytes during galvanotaxis and that directional migration and migration speed are probably controlled by separate mechanisms. J. Cell. Physiol. 193: 1–9, 2002. © 2002 Wiley‐Liss, Inc.