Modulation of epithelial Na+ channel activity by long-chain n-3 fatty acids.
The epithelial sodium channel is found in apical membranes of a variety of native epithelial tissues, where it regulates sodium and fluid balance. In vivo, a number of hormones and other endogenous factors, including polyunsaturated fatty acids (PUFAs), regulate these channels. We tested the effects of essential n-3 and n-6 PUFAs on amiloride-sensitive sodium transport in A6 epithelial cells. Eicosapentaenoic acid [EPA; C20:5(n-3)] transiently stimulated amiloride-sensitive open-circuit current (I(Na)) from 4.0 +/- 0.3 to 7.7 +/- 0.3 microA/cm2 within 30 min (P < 0.001). No activation was seen in the presence of 10 microM amiloride. In cell-attached but not in cell-excised patches, EPA acutely increased the open probability of sodium channels from 0.45 +/- 0.08 to 0.63 +/- 0.10 (P = 0.02, paired t-test). n-6 PUFAs, including linoleic acid (C18:2), eicosatetraynoic acid (C20:4), and docosapentanoic acid (C22:5) had no effect, whereas n-3 docosahexanoic acid (C22:6) activated amiloride-sensitive I(Na) in a manner similar to EPA. Activation of I(Na) by EPA was prevented by H-89, a PKA inhibitor. Similarly, PKA activity was stimulated by EPA. Nonspecific stimulation of phosphodiesterase activity by CoCl2 completely prevented the effect of EPA on sodium transport. We conclude that n-3 PUFAs activate epithelial sodium channels downstream of cAMP in a cAMP-dependent pathway also involving PKA.
Mies
Frédérique
F
Physiology Department, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Shlyonsky
Vadim
V
Goolaerts
Arnaud
A
Sariban-Sohraby
Sarah
S
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology; D014982:Xenopus laevis
D004232:Diuretics; D053503:Epithelial Sodium Channels; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D015222:Sodium Channels; D000584:Amiloride; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases