Lysophosphatidic Acid Sensitises Ca 2+ Influx through Mechanosensitive Ion Channels in Cultured Lens Epithelial Cells

Abstract

We investigated the effect of lysophosphatidic acid (LPA), a bioactive phospholipid, on the response in cytosolic free Ca 2+ concentration ([Ca 2+] i) to mechanical stress in cultured bovine lens epithelial cells. Spritzing of bath solution onto cells as mechanical stress caused marked increase in [Ca 2+] i in the presence of LPA and this increase was concentration-dependent (1–10 μM), whereas neither addition of LPA alone nor the mechanical stress in the absence of LPA affected [Ca 2+] i. The mechanical stress-induced increase in [Ca 2+] i in the presence of LPA was inhibited by removing extracellular Ca 2+ or by addition of Gd 3+, a blocker of mechanosensitive cation channels, but not by nicardipine, thapsigargin, an inhibitor of endoplasmic reticulum-ATPase pump, or U73122, a phospholipase C inhibitor. These results show that LPA sensitises Ca 2+ influx through cation-selective mechanosensitive channels, but does not sensitise Ca 2+ release from intracellular stores, triggered by changes in mechanical stress. On the other hand, phosphatidic acid had less of a sensitising effect than LPA, and neither lysophosphatidylcholine nor chlorpromazine had any effect. Also Ca 2+ mobilising agonists, ATP, histamine and carbachol, did not sensitise Ca 2+ response to the mechanical stress. These results show that LPA sensitises mechanoreceptor-linked response in lens epithelial cells, suggesting that it plays a role in the development of cataracts due to increases in [Ca 2+] i induced by mechanical stress.