Journal article
Activation of endothelial IKCa channels underlies NO-dependent myoendothelial feedback
Vascular Pharmacology, Vol.74, pp.130-138
2015
Abstract
Agonist-induced vasoconstriction triggers a negative feedback response whereby movement of charged ions through gap junctions and/or release of endothelium-derived (NO) limit further reductions in diameter, a mechanism termed myoendothelial feedback. Recent studies indicate that electrical myoendothelial feedback can be accounted for by flux of inositol trisphosphate (IP3) through myoendothelial gap junctions resulting in localized increases in endothelial Ca2 + to activate intermediate conductance calcium-activated potassium (IKCa) channels, the resultant hyperpolarization then conducting back to the smooth muscle to attenuate agonist-induced depolarization and tone. In the present study we tested the hypothesis that activation of IKCa channels underlies NO-mediated myoendothelial feedback. Functional experiments showed that block of IP3 receptors, IKCa channels, gap junctions and transient receptor potential canonical type-3 (TRPC3) channels caused endothelium-dependent potentiation of agonist-induced increase in tone which was not additive with that caused by inhibition of NO synthase supporting a role for these proteins in NO-mediated myoendothelial feedback. Localized densities of IKCa and TRPC3 channels occurred at the internal elastic lamina/endothelial-smooth muscle interface in rat basilar arteries, potential communication sites between the two cell layers. Smooth muscle depolarization to contractile agonists was accompanied by IKCa channel-mediated endothelial hyperpolarization providing the first demonstration of IKCa channel-mediated hyperpolarization of the endothelium in response to contractile agonists. Inhibition of IKCa channels, gap junctions, TRPC3 channels or NO synthase potentiated smooth muscle depolarization to agonists in a non-additive manner. Together these data indicate that rather being distinct pathways for the modulation of smooth muscle tone, NO and endothelial IKCa channels are involved in an integrated mechanism for the regulation of agonist-induced vasoconstriction.
Details
- Title
- Activation of endothelial IKCa channels underlies NO-dependent myoendothelial feedback
- Authors
- Paul M Kerr (Author) - MacEwan University, CanadaRan Wei (Author) - University of Alberta, CanadaRaymond Tam (Author) - University of Alberta, CanadaShaun L Sandow (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and EngineeringTimothy V Murphy (Author) - University of New South WalesKatarina Ondrusova (Author) - University of Alberta, CanadaStephanie E Lunn (Author) - University of Alberta, CanadaCam Ha T Tran (Author) - University of Calgary, CanadaDonald G Welsh (Author) - University of Calgary, CanadaFrances Plane (Author) - University of Alberta, Canada
- Publication details
- Vascular Pharmacology, Vol.74, pp.130-138
- Publisher
- Elsevier Inc.
- Date published
- 2015
- DOI
- 10.1016/j.vph.2015.09.001
- ISSN
- 1537-1891
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99450182102621
- Output Type
- Journal article
Metrics
18 File views/ downloads
961 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Pharmacology & Pharmacy
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites