Document Detail

Maternal high-altitude hypoxia and suppression of ryanodine receptor-mediated Ca2+ sparks in fetal sheep pulmonary arterial myocytes.
MedLine Citation:
PMID:  22962012     Owner:  NLM     Status:  MEDLINE    
Ca(2+) sparks are fundamental Ca(2+) signaling events arising from ryanodine receptor (RyR) activation, events that relate to contractile and dilatory events in the pulmonary vasculature. Recent studies demonstrate that long-term hypoxia (LTH) can affect pulmonary arterial reactivity in fetal, newborn, and adult animals. Because RyRs are important to pulmonary vascular reactivity and reactivity changes with ontogeny and LTH we tested the hypothesis that RyR-generated Ca(2+) signals are more active before birth and that LTH suppresses these responses. We examined these hypotheses by performing confocal imaging of myocytes in living arteries and by performing wire myography studies. Pulmonary arteries (PA) were isolated from fetal, newborn, or adult sheep that lived at low altitude or from those that were acclimatized to 3,801 m for > 100 days. Confocal imaging demonstrated preservation of the distance between the sarcoplasmic reticulum, nucleus, and plasma membrane in PA myocytes. Maturation increased global Ca(2+) waves and Ca(2+) spark activity, with sparks becoming larger, wider, and slower. LTH preferentially depressed Ca(2+) spark activity in immature pulmonary arterial myocytes, and these sparks were smaller, wider, and slower. LTH also suppressed caffeine-elicited contraction in fetal PA but augmented contraction in the newborn and adult. The influence of both ontogeny and LTH on RyR-dependent cell excitability shed new light on the therapeutic potential of these channels for the treatment of pulmonary vascular disease in newborns as well as adults.
Scott R Hadley; Quintin Blood; Monica Rubalcava; Edith Waskel; Britney Lumbard; Petersen Le; Lawrence D Longo; John N Buchholz; Sean M Wilson
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-09-07
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  303     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-01-03     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L799-813     Citation Subset:  IM    
Center for Perinatal Biology, Loma Linda University, California 92350, USA.
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MeSH Terms
Analysis of Variance
Caffeine / pharmacology
Calcium Channel Agonists / pharmacology
Calcium Signaling*
Cell Hypoxia
Cell Membrane / metabolism
Fetus / cytology,  metabolism,  physiopathology
Muscle Contraction / drug effects
Myocytes, Smooth Muscle / metabolism*,  physiology
Potassium / metabolism,  physiology
Pulmonary Artery / cytology*,  physiopathology
Ryanodine / pharmacology
Ryanodine Receptor Calcium Release Channel / metabolism*,  physiology
Sarcoplasmic Reticulum / metabolism
Statistics, Nonparametric
Grant Support
5-P20-MD-001632/MD/NIMHD NIH HHS; 52006309//Howard Hughes Medical Institute; HD-069746/HD/NICHD NIH HHS; HD-31226/HD/NICHD NIH HHS; HD/HL-03807/HD/NICHD NIH HHS; P01 HD031226/HD/NICHD NIH HHS; R01 HD003807/HD/NICHD NIH HHS; R03 HD069746/HD/NICHD NIH HHS
Reg. No./Substance:
0/Calcium Channel Agonists; 0/Ryanodine Receptor Calcium Release Channel; 15662-33-6/Ryanodine; 58-08-2/Caffeine; 7440-09-7/Potassium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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