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Differential alterations in gap junction and calcium-activated potassium channel expression and activity in gut and skeletal muscle arteries in obesity
Abstract   Peer reviewed

Differential alterations in gap junction and calcium-activated potassium channel expression and activity in gut and skeletal muscle arteries in obesity

Shaun L Sandow, R E Haddock and P S Chadha
Journal of Vascular Research, Vol.46(Supplement 2), p.6
Australian and New Zealand Microcirculation Society Meeting, 14th (Queenstown, New Zealand, 25-Aug-2009–27-Aug-2009)
2009
DOI: https://doi.org/10.1159/000230992
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https://doi.org/10.1159/000230992View
Published Version

Abstract

Medical and Health Sciences endothelium-dependent relaxation hyperpolarization diet-induced obesity
Endothelium-dependent relaxation due to nitric oxide (NO), prostacyclin (PGI2) and non- NO/PGI2 endothelium-derived hyperpolarization is critical for control of blood flow and pressure. In rat mesenteric artery, endothelium-derived hyperpolarization depends on microdomain signalling at close (less than 30nm) contacts of endothelial and smooth muscle cells and involve transfer of current and/or localized K+ activity [1]. In close proximity at such sites, connexins 37/40, intermediate conductance calcium-activated potassium channels (IKCa), endoplasmic reticulum inositol 1,4,5-trisphosphate receptors are present [2], with functional data suggesting interaction [1, 3]. Further anatomical data suggests that transient receptor potential canonical type 3 channels are also present at such sites (see Senadheera et al. abstract in this ANZMS Proceedings Issue). This study determines the characteristics of microdomain-dependent endothelium-derived hyperpolarization in control (536±7g) and high fat cafe diet-induced obese (723±15g) rat mesenteric and saphenous artery (n=45, each). Western blotting, conventional and ultrastructural immunohistochemistry and concomitant pressure myography and sharp electrode membrane potential recording characterizedanatomical and functional relaxation properties. In control rat mesenteric artery, small and IKCa and myoendothelial gap junction activity account for endothelium-derived hyperpolarization. Myoendothelial gap junction density and activity is the same in control and obese, whilst in obese, differential IKCa activation and distribution account for altered endothelium-derived hyperpolarization. In control and obese rat saphenous artery, AChmediated relaxation is maintained. In control, such relaxation is entirely NO-mediated, whereas in obese, the NO contribution is impaired, and IKCa and myoendothelial gap junction upregulation correspond with distinct contributions to endothelium-dependent relaxation. Data suggest that myoendothelial microdomain signalling sites are required for endotheliumderived hyperpolarization and associated relaxation in rat resistance arteries, and that alteration in the anatomy of these sites in a rodent model of diet-induced obesity corresponds with altered function. Subsequent studies in intact animals will investigate whether the manipulation of myoendothelial microdomain signalling sites represents a target to control blood flow and thereby vascular disease, such as that present in obesity

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