title: Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets.
abstract: BACKGROUND
  The most common CF-causing mutations interfere with CFTR trafficking from the endoplasmic reticulum (CFTR-F508del) or prematurely terminate transcription (CFTR-null). We suspected that genotype-specific patterns of CFTR expression would have differential effects on smooth muscle cell calcium signaling and hence vascular tone. We hypothesized that compared to wild-type or CFTR-null aorta, aorta from CFTR-F508del (dF) piglets will have reduced endoplasmic reticulum calcium mobilization and decreased vasoconstriction.
  
  
  METHODS
  Aortic reactivity was assessed by myography, and ratiometric calcium imaging was performed in isolated vascular smooth muscle cells.
  
  
  RESULTS
  Aorta from dF piglets had reduced myogenic tone (P<0.001) and decreased constriction to KCl (P<0.05). Combined inhibition of ryanodine and IP3 receptors decreased wild-type and CFTR-null responses to levels seen in dF aorta. Compared to wild-type cells, dF-expressing smooth muscle cells had reduced calcium transients, while CFTR-null cells had decreased baseline intracellular calcium concentrations.
  
  
  CONCLUSIONS
  Expression of CFTR-F508del interferes with smooth muscle cell calcium handling and decreases aortic responsiveness.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Jinny J
authors.initials: JJ
authors.lastname: Guo
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Vivian
authors.initials: V
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Volk
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Segar
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States. Electronic address: robert-roghair@uiowa.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005838:Genotype; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009213:Myography; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Cystic fibrosis transmembrane conductance regulator; Endoplasmic reticulum; Inositol triphosphate receptor; Vascular smooth muscle cell