8-isoprostaglandin E(2) activates Ca(2+)-dependent K(+) current via cyclic AMP signaling pathway in murine renal artery.

The inhibitory pathway of 8-isoprostaglandin E(2) was investigated in murine renal arterial smooth muscle. K(+) current was augmented in a concentration-dependent fashion, with an average increase of 123+/-28% (n=6) following application of 10(-5) M 8-iso PGE(2). This augmentation was observed in the presence of 4-aminopyridine (4-AP, 10(-3) M) but not that of charybdotoxin (Ch Tx, 10(-7) M). Fluorimetric recordings showed marked concentration-dependent increase of cytosolic Ca(2+) levels by 8-iso PGE(2), while an enzyme-linked immunosorbent assay (ELISA)-based cyclic AMP assay showed increased cAMP levels by 10(-7) M 8-iso PGE(2) challenge. The isoprostane-induced augmentation was prevented by the ryanodine receptor blocker ruthenium red (10(-5) M) or the adenylate cyclase blocker SQ 22536 (10(-4) M). The protein kinase A (PKA) inhibitor H 89 (10(-5) M) inhibited resting K(+) currents (78+/-5%, n=5) but did not prevent 8-iso PGE(2) from augmenting the remaining K(+) current. We conclude that 8-iso PGE(2) enhances Ca(2+)-dependent K(+) currents in murine renal artery through a cAMP-dependent pathway which may involve internally sequestered Ca(2+).