IngentaConnect Role of arachidonic acid in hyposmotic membrane stretch-induced i...

Authors: YANG, Meng¹; LI, Xing-lan²; XU, Hui-ying²; SUN, Jia-bin²; MEI, Bin³; ZHENG, Hai-feng²; PIAO, Lian-hua²; XING, De-gang²; LI, Zhai-liu²; XU, Wen-xie¹

Source: Acta Pharmacologica Sinica, Volume 26, Number 10, October 2005 , pp. 1233-1242(10)

Publisher: Blackwell Publishing

Abstract:

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 A₂. 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 A₂, which hydrolyzes membrane phospholipids to ultimately produce AA; AA as a second messenger mediates Ca²⁺ influx, which triggers Ca²⁺-induced Ca²⁺ release and elicits activation ofI_K(Ca) in gastric antral circular myocytes of the guinea pig.

Keywords: gastric myocyte; arachidonic acid; hyposmotic membrane stretch; calcium-activated potassium current

Document Type: Research article

DOI: 10.1111/j.1745-7254.2005.00201.x

Affiliations: 1: Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200030; 2: Department of Physiology, Yanbian University College of Medicine, Yanji 133000; 3: East China Normal University School of Life Science, Shanghai 200062, China

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Role of arachidonic acid in hyposmotic membrane stretch-induced increase in calcium-activated potassium currents in gastric myocytes