Acta Pharmacologica Sinica 2005 October; 26 (10): 1233-1242; doi: 10.1111/j.1745-7254.2005.00201.x

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 µmol/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).

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 of I_K(Ca) in gastric antral circular myocytes of the guinea pig.

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