Mechanism of rat mesenteric arterial KATP channel activation by 14,15-epoxyeicosatrienoic acid

American Journal of Physiology. Heart and Circulatory Physiology
Dan YeHon-Chi Lee

Abstract

Recently, we reported that 11,12-epoxyeicosatrienoic acid (11,12-EET) potently activates rat mesenteric arterial ATP-sensitive K(+) (K(ATP)) channels and produces significant vasodilation through protein kinase A-dependent mechanisms. In this study, we tried to further delineate the signaling steps involved in the activation of vascular K(ATP) channels by EETs. Whole cell patch-clamp recordings [0.1 mM ATP in the pipette, holding potential (HP) = 0 mV and testing potential (TP) = -100 mV] in freshly isolated rat mesenteric smooth muscle cells showed small glibenclamide-sensitive K(ATP) currents (19.0 +/- 7.9 pA, n = 5) that increased 6.9-fold on exposure to 5 microM 14,15-EET (132.0 +/- 29.0 pA, n = 7, P < 0.05 vs. control). With 1 mM ATP in the pipette solution, K(ATP) currents (HP = 0 mV and TP = -100 mV) were increased 3.5-fold on exposure to 1 microM 14,15-EET (57.5 +/- 14.3 pA, n = 9, P < 0.05 vs. baseline). In the presence of 100 nM iberiotoxin, 1 microM 14,15-EET hyperpolarized the membrane potential from -20.5 +/- 0.9 mV at baseline to -27.1 +/- 3.0 mV (n = 6 for both, P < 0.05 vs. baseline), and the EET effects were significantly reversed by 10 microM glibenclamide (-21.8 +/- 1.4 mV, n = 6, P < 0.05 vs. EET). Incubatio...Continue Reading

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Mar 12, 2005·The Journal of Biological Chemistry·Tong LuHon-Chi Lee

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Citations

Mar 13, 2010·Pflügers Archiv : European journal of physiology·William B Campbell, Ingrid Fleming
Jun 15, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jeffrey J OlearczykJohn D Imig
Sep 29, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Dovenia S PonnothS Jamal Mustafa
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Feb 28, 2021·Signal Transduction and Targeted Therapy·Bei WangDao Wen Wang
Aug 23, 2011·Prostaglandins & Other Lipid Mediators·Karen WagnerBruce D Hammock

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