Open AccessRole of arachidonic acid in hyposmotic membrane stretch‐induced increase in calcium‐activated potassium currents in gastric myocytes 1
Author(s) -
YANG Meng,
LI Xinglan,
XU Huiying,
SUN Jiabin,
MEI Bin,
ZHENG Haifeng,
PIAO Lianhua,
XING Degang,
LI Zhailiu,
XU Wenxie
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00201.x
Subject(s) - chemistry , medicine , endocrinology , phospholipase a2 , arachidonic acid , calcium , nordihydroguaiaretic acid , ryanodine receptor , phospholipase c , biophysics , biochemistry , biology , receptor , organic chemistry , enzyme
Aim: To study effects of arachidonic acid (AA) and its metabolites on the hyposmotic membrane stretch‐induced increase in calcium‐activated potassium currents (I KCa ) in gastric myocytes. Methods: Membrane currents were recorded by using a conventional whole cell patch‐clamp technique in gastric myocytes isolated with collagenase. Results: Hyposmotic membrane stretch and AA increased both I K(Ca) and spontaneous transient outward currents significantly. Exogenous AA could potentiate the hyposmotic membrane stretch‐induced increase in I K(Ca ). The hyposmotic membrane stretch‐induced increase in I K(Ca) was significantly suppressed by dimethyleicosadienoic acid (100 umol/L in pipette solution), an inhibitor of phospholipase A 2 . Nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly suppressed AA and hyposmotic membrane stretch‐induced increases inI K(Ca) . External calcium‐free or gadolinium chloride, a blocker of stretch‐activated channels, blocked the AA‐induced increase in I K(Ca) significantly, but it was not blocked by nicardipine, an L‐type calcium channel blocker. Ryanodine, a calcium‐induced calcium release agonist, completely blocked the AA‐induced increase inI K(Ca) ; however, heparin, a potent inhibitor of inositol triphosphate receptor, did not block the AA‐induced increase in I K(Ca) . Conclusion: Hyposmotic membrane stretch may activate phospholipase A 2 , which hydrolyzes membrane phospholipids to ultimately produce AA; AA as a second messenger mediates Ca 2+ influx, which triggers Ca 2+ ‐induced Ca 2+ release and elicits activation ofI K(Ca) in gastric antral circular myocytes of the guinea pig.