Arachidonic acid inhibits the secretory K+ channel of cortical collecting duct of rat kidney.
We used the patch-clamp technique to study the effects of arachidonic acid (AA) on the 35-pS secretory K+ channel in the apical membrane of rat cortical collecting duct (CCD). Application of 10 microM AA reversibly reduced channel activity to 1% of the control value [sum of open probability (NPo) decreased from 3.8 to 0.04]. AA inhibits the apical 35-pS K+ channel directly, because application of indomethacin (an inhibitor of cyclooxygenase), nordihydroguaiaretic acid (an enzyme inhibitor of lipoxygenase), and clotrimazole (an inhibitor of epoxygenase) failed to antagonize the AA-induced blocking effect on K+ channel activity. Oleic acid, a cis-unsaturated acid, also blocks K+ channel activity. However, the inhibitory constant (Ki) of oleic acid (5.1 microM) is significantly higher than that of AA (2.6 microM). These results indicate that AA and cis-unsaturated fatty acids are involved in downregulating the apical secretory K+ channel of rat CCD.
Wang
W
W
Department of Cellular and Molecular Physiology, Yale University Medical School, New Haven, Connecticut 06510.
Cassola
A
A
Giebisch
G
G
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D003022:Clotrimazole / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D009829:Oleic Acids; D015221:Potassium Channels; D016718:Arachidonic Acid; D019301:Oleic Acid; D009637:Masoprocol; D003022:Clotrimazole; D007213:Indomethacin