Role of arachidonic acid in hyposmotic membrane stretch-induced increase in calcium-activated potassium currents in gastric myocytes.
OBJECTIVE
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 micromol/L in pipette solution), an inhibitor of phospholipase A2. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly suppressed AA and hyposmotic membrane stretch-induced increases in I(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 in I(K(Ca)); however, heparin, a potent inhibitor of inositol triphosphate receptor, did not block the AA-induced increase in I(K(Ca)).


CONCLUSIONS
Hyposmotic membrane stretch may activate phospholipase A2, 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 of I(K(Ca)) in gastric antral circular myocytes of the guinea pig.
Yang
Meng
M
Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
Li
Xing-lan
XL
Xu
Hui-ying
HY
Sun
Jia-bin
JB
Mei
Bin
B
Zheng
Hai-feng
HF
Piao
Lian-hua
LH
Xing
De-gang
DG
Li
Zhai-liu
ZL
Xu
Wen-xie
WX
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000502:physiology; D002469:Cell Separation; D005682:Gadolinium / Q000494:pharmacology; D006168:Guinea Pigs; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D009997:Osmotic Pressure; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*; D012433:Ryanodine / Q000494:pharmacology; D013270:Stomach / Q000166:cytology / Q000502:physiology*
D016859:Lipoxygenase Inhibitors; D024681:Potassium Channels, Calcium-Activated; D012433:Ryanodine; D016718:Arachidonic Acid; D009637:Masoprocol; D005682:Gadolinium; C038958:gadolinium chloride