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 various transport processes, including conductive chloride transport in brush border membranes in the human placenta. The purpose of this work was to explore the effects of some cis unsaturated fatty acids on the electrophysiologic properties of the maxi chloride channels present in apical membranes from human placenta.


METHODS
Apical membrane chloride channels from human term placentas were reconstituted in giant liposomes. These cell-sized liposomes, generated by a cycle of dehydration and rehydration, are suitable for electrophysiologic studies by the patch-clamp method.


RESULTS
Low micromolar concentrations of arachidonic acid reversibly inhibit maxi chloride channels in excised patches. Other cis unsaturated fatty acids, such as oleic and linoleic acids, show similar blockade. The inhibition 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 electrophysi ologic counterpart of 4,4 -diisothiocyanatostilbene-2, 2 -disulfonic acid and cis unsaturated fatty acid-inhibited conductance previously described in brush border membranes of the human placenta. From a functional point of view the control of these channels by arachidonic acid may be of great importance in placental physiologic characteristics. Regulation of chloride channels could be important in the control of electrolyte and fluid transfer across the placenta. In addition, if these channels contribute to setting the membrane potential their regulation could have consequences for nutrient transport and delivery to the fetus. The electrophysiologic identification of these channels and their regulation might help to unravel their possible role in transplacental transport in normal and pathologic placental tissue.
Riquelme
G
G
Programa de Fisiología y Biofísica, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile.
Parra
M
M
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D004553:Electric Conductivity; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010920:Placenta / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy