| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Departments of Physiology and 2 Medicine, Division of Rheumatology, The University of Tennessee Health Science Center, Memphis, Tennessee.
PURPOSE. This study was designed to examine the effects of lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) on Cl- currents (IClLPA) in cultured corneal keratocytes isolated from the corneas of New Zealand White rabbits.
METHODS. IClLPA and resting voltages were recorded with the amphotericin perforated-patch technique. Phenotype was determined with antibodies to 
-smooth muscle actin.
RESULTS. Keratocytes cultured in serum have a phenotype (myofibroblast) and ionic currents similar to those of keratocytes isolated directly from corneas during wound healing. LPA and S1P both activated IClLPA in a dose-dependent manner, and the LPA receptor–specific antagonist dioctyl-glycerol pyrophosphate (DGPP) blocked the LPA response, but not the S1P response. In addition, a relatively inactive form of LPA (LPA 8:0) was relatively ineffective in activating IClLPA. Activation of IClLPA significantly depolarized the cells, and this depolarization was reversed by blocking IClLPA with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB).
CONCLUSIONS. These results demonstrate that activation of IClLPA by LPA in cultured corneal keratocytes is receptor mediated and that IClLPA can also be activated by S1P. From a functional standpoint, this work confirms that the current, which is typically thought of as purely volume-activated, can be activated through a receptor. In addition, activation of IClLPA results in depolarization of the keratocyte. Finally, this work demonstrates that cultured corneal keratocytes can act as a model for the study of ion channel function in keratocytes during corneal wound healing.
This article has been cited by other articles:
|
|
 |
|
  Z. Yin, Y. Tong, H. Zhu, and M. A. Watsky ClC-3 is required for LPA-activated Cl- current activity and fibroblast-to-myofibroblast differentiation Am J Physiol Cell Physiol, February 1, 2008; 294(2): C535 - C542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, Z. Liu, and K. E. Meier Lysophosphatidic acid as a mediator for proinflammatory agonists in a human corneal epithelial cell line Am J Physiol Cell Physiol, November 1, 2006; 291(5): C1089 - C1098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Kim, G. H. Liang, J. A. Kim, Y. J. Kim, S. Oh, and S. H. Suh Sphingosine-1-phosphate activates BKCa channels independently of G protein-coupled receptor in human endothelial cells Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1000 - C1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Yin and M. A. Watsky LPA and S1P Increase Corneal Epithelial and Endothelial Cell Transcellular Resistance Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 1927 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Danieli-Betto, E. Germinario, A. Esposito, A. Megighian, M. Midrio, B. Ravara, E. Damiani, L. D. Libera, R. A. Sabbadini, and R. Betto Sphingosine 1-phosphate protects mouse extensor digitorum longus skeletal muscle during fatigue Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1367 - C1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yin and M. A. Watsky Chloride channel activity in human lung fibroblasts and myofibroblasts Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1110 - L1116. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
