title: Functional Tuning of Intrinsic Endothelial Ca2+ Dynamics in Swine Coronary Arteries.
abstract: BACKGROUND
  Recent data from mesenteric and cerebral beds have revealed spatially restricted Ca(2+) transients occurring along the vascular intima that control effector recruitment and vasodilation. Although Ca(2+) is pivotal for coronary artery endothelial function, spatial and temporal regulation of functional Ca(2+) signals in the coronary endothelium is poorly understood.
  
  
  OBJECTIVE
  We aimed to determine whether a discrete spatial and temporal profile of Ca(2+) dynamics underlies endothelium-dependent relaxation of swine coronary arteries.
  
  
  RESULTS
  Using confocal imaging, custom automated image analysis, and myography, we show that the swine coronary artery endothelium generates discrete basal Ca(2+) dynamics, including isolated transients and whole-cell propagating waves. These events are suppressed by depletion of internal stores or inhibition of inositol 1,4,5-trisphosphate receptors but not by inhibition of ryanodine receptors or removal of extracellular Ca(2+). In vessel rings, inhibition of specific Ca(2+)-dependent endothelial effectors, namely, small and intermediate conductance K(+) channels (K(Ca)3.1 and K(Ca)2.3) and endothelial nitric oxide synthase, produces additive tone, which is blunted by internal store depletion or inositol 1,4,5-trisphosphate receptor blockade. Stimulation of endothelial inositol 1,4,5-trisphosphate-dependent signaling with substance P causes idiosyncratic changes in dynamic Ca(2+) signal parameters (active sites, event frequency, amplitude, duration, and spatial spread). Overall, substance P-induced vasorelaxation corresponded poorly with whole-field endothelial Ca(2+) measurements but corresponded precisely with the concentration-dependent change in Ca(2+) dynamics (linearly translated composite of dynamic parameters).
  
  
  CONCLUSIONS
  Our findings show that endothelium-dependent control of swine coronary artery tone is determined by spatial and temporal titration of inherent endothelial Ca(2+) dynamics that are not represented by tissue-level averaged Ca(2+) changes.
authors.affiliation: From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile.
authors.forename: Michael
authors.initials: M
authors.lastname: Francis
authors.affiliation: From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Waldrup
authors.affiliation: From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile.
authors.forename: Xun
authors.initials: X
authors.lastname: Qian
authors.affiliation: From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Solodushko
authors.affiliation: From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile.
authors.forename: John
authors.initials: J
authors.lastname: Meriwether
authors.affiliation: From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile. mtaylor@southalabama.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D007091:Image Processing, Computer-Assisted; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects / Q000502:physiology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D007537:Isometric Contraction; D008297:Male; D018613:Microscopy, Confocal; D008955:Models, Cardiovascular; D009213:Myography; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D010455:Peptides; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D034421:Sus scrofa; D013552:Swine; D017539:Tunica Intima / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D051640:Small-Conductance Calcium-Activated Potassium Channels; C582897:vasorelaxin protein, Odorrana schmackeri; D013373:Substance P; D052250:Nitric Oxide Synthase Type III; D002118:Calcium
keywords: calcium signaling; coronary vessels; myography; potassium channels; substance P
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