Dc. Devor et Ra. Frizzell, MODULATION OF K-ACID IN T84 CELLS - I - INHIBITION OF THE CA2+-DEPENDENT K+ CHANNEL( CHANNELS BY ARACHIDONIC), American journal of physiology. Cell physiology, 43(1), 1998, pp. 138-148
The Cl- secretory response of colonic cells to Ca2+-mediated agonists
is transient despite a sustained elevation of intracellular Ca2+. We e
valuated the effects of second messengers proposed to limit Ca2+-media
ted Cl- secretion on the basolateral membrane, Ca2+-dependent K+ chann
el (K-Ca) in colonic secretory cells, T84. Neither protein kinase C (P
KC) nor inositol tetrakisphosphate (1,3,4,5 or 3,4,5,6 form) affected
K-Ca in excised inside-out patches. In contrast, arachidonic acid (AA;
3 mu M) potently inhibited K-Ca, reducing NPo, the product of number
of channels and channel open probability, by 95%. The apparent inhibit
ion constant for this AA effect was 425 nM. AA inhibited K-Ca in the p
resence of both indomethacin and nordihydroguaiaretic acid, blockers o
f the cyclooxygenase and lipoxygenase pathways. In the presence of alb
umin, the effect of AA on K-Ca was reversed. A similar effect of AA wa
s observed on K-Ca during outside-out recording. We determined also th
e effect of the cis-unsaturated fatty acid linoleate, the trans-unsatu
rated fatty acid elaidate, and the saturated fatty acid myristate. At
3 mu M, all of these fatty acids inhibited K-Ca, reducing NPo by 72-86
%. Finally, the effect of the cytosolic phospholipase A(2) inhibitor a
rachidonyltrifluoromethyl ketone (AACOCF(3)) on the carbachol-induced
short-circuit current (I-sc) response was determined. In the presence
of AACOCF(3), the peak carbachol-induced I-sc response was increased s
imilar to 2.5-fold. Our results suggest that AA generation induced by
Ca2+-mediated agonists may contribute to the dissociation observed bet
ween the rise in intracellular Ca2+ evoked by these agonists and the a
ssociated Cl- secretory response.