Faculty Collaboration Database

Apamin-sensitive K+ currents mediate arachidonic acid-induced relaxations of rabbit aorta. Hypertension 2004 Feb;43(2):413-9

Date

12/24/2003

Pubmed ID

14691199

DOI

10.1161/01.HYP.0000110945.84443.d2

Scopus ID

2-s2.0-0842268281 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

Arachidonic acid induces an endothelium-dependent relaxation of the rabbit aorta that is blocked by lipoxygenase inhibitors. The cellular vasodilatory mechanisms activated by arachidonic acid metabolites remain undefined. In rabbit thoracic aortic rings pretreated with indomethacin (10 micromol/L) and contracted with phenylephrine, arachidonic acid (0.1 to 100 micromol/L) induced concentration-dependent relaxations. Maximal relaxations averaged 45+/-3% and were inhibited by increasing extracellular K+ (30 mmol/L, 15+/-5%; P<0.001) or incubation with apamin (100 nmol/L, 26+/-7%; P<0.05) but not incubation with charybdotoxin (100 nmol/L, 41+/-5%). In aortic strips with an intact endothelium that were treated with phenylephrine, arachidonic acid (10 micromol/L) increased the membrane potential from -28.7+/-1.3 to -37.8+/-3.0 mV (P<0.01). Preincubation with apamin did not alter basal membrane potential but inhibited arachidonic acid-induced hyperpolarization (-31.5+/-1.5 mV). Incubation of rabbit aortic segments with apamin or charybdotoxin did not alter [14C]arachidonic acid metabolism. Whole-cell outward K+ currents from isolated rabbit aortic smooth muscle cells averaged 43.0+/-4.8 pA/pF at 60 mV and were significantly decreased to 35.7+/-4.2 pA/pF by apamin (P<0.001). Subsequent addition of charybdotoxin further decreased maximal currents to 14.4+/-2.3 pA/pF. Addition of 11,12,15-trihydroxyeicosatrienoic acid increased the outward whole-cell K+ current. In inside-out patches of aortic smooth muscle, apamin inhibited the calcium activation (100 to 300 nmol/L; P<0.001) of a small-conductance K+ channel (approximately 24 pS). These results suggest that arachidonic acid induces endothelium-dependent hyperpolarization and relaxation of rabbit aorta through activation of smooth muscle, apamin-sensitive K+ currents.

Author List

Gauthier KM, Spitzbarth N, Edwards EM, Campbell WB

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Apamin
Arachidonic Acid
Culture Techniques
Electric Conductivity
Male
Membrane Potentials
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Potassium Channels
Rabbits
Vasodilation