Regulation of human placental chloride channel by arachidonic acid and other cis unsaturated fatty acids

OBJECTIVE: Arachidonic acid has been implicated in the modulation of variou s transport processes, including conductive chloride transport in brush bor der membranes in the human placenta. The purpose of this work was to explor e the effects of some cis unsaturated fatty acids on the electrophysiologic properties of the maxi chloride channels present in apical membranes from human placenta. STUDY DESIGN: Apical membrane chloride channels from human term placentas w ere reconstituted in giant liposomes. These cell-sized liposomes, generated by a cycle of dehydration and rehydration, are suitable for electrophysiol ogic studies by the patch-clamp method. RESULTS: Low micromolar concentrations of arachidonic acid reversibly inhib it maxi chloride channels in excised patches. Other cis unsaturated fatty a cids, such as oleic and linoleic acids, show similar blockade. The inhibiti on was dose dependent. The maxi chloride channel can also be inhibited by 4 ,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a known chloride channel inhibitor. CONCLUSIONS: Our results identify the apical membrane maxi chloride channel as a possible electrophysiologic counterpart of 4,4'-diisothiocyanatostilb ene-2,2'-disulfonic acid and cis unsaturated fatty acid-inhibited conductan ce previously described in brush border membranes of the human placenta. Fr om a functional point of view the control of these channels by arachidonic acid may be of great importance in placental physiologic characteristics. R egulation of chloride channels could be important in the control of electro lyte and fluid transfer across the placenta. In addition, if these channels contribute to setting the membrane potential their regulation could have c onsequences for nutrient transport and delivery to the fetus. The electroph ysiologic identification of these channels and their regulation might help to unravel their possible role in transplacental transport in normal and pa thologic placental tissue.