Direct modulation of secretory chloride channels by arachidonic and other cis unsaturated fatty acids

The effect of fatty acids on Cl- channels and transepithelial Cl- secretion is investigated. Patch-clamp experiments show that arachidonic acid blocks Cl- channels in a dose-dependent manner. Kinetic analysis shows that the mean open time is decreased 10-fold with 25 microM arachidonic acid. There is a linear relationship between the reciprocal of mean open time and blocker concentration within the range of 1 to 25 microM. The reciprocal of mean blocked time does not change with arachidonic acid concentration. Other cis unsaturated fatty acids, including oleic, linoleic, and ricinoleic acids, demonstrate similar blocks. Trans unsaturated acids such as elaidic acid and saturated fatty acids, including stearic, palmitic, and myristic acids, do not inhibit the channel at 20 microM. Ricinoleic acid decreases short circuit current in T84 cells, a colonic carcinoma cell line that secretes Cl-. Our results suggest that the direct effect of arachidonic and other fatty acids on Cl- secretion is to block Cl- channel current.