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Chronic hypoxia modulates relations among calcium, myosin light chain phosphorylation, and force differently in fetal and adult ovine basilar arteries

Chronic hypoxia modulates relations among calcium, myosin light chain phosphorylation, and force... The present study tests the hypothesis that age-related differences in contractility of cerebral arteries from hypoxic animals involve changes in myofilament Ca 2+ sensitivity. Basilar arteries from term fetal and nonpregnant adult sheep maintained 110 days at 3,820 m were used in measurements of cytosolic calcium concentration (Ca 2+ i ), myosin light chain phosphorylation, and contractile tensions induced by graded concentrations of K + or serotonin (5-HT). Slopes relating Ca 2+ i to tension were similar in fetal (0.83 ± 0.07) and adult (1.02 ± 0.08) arteries for K + contractions but were significantly greater for fetal (3.77 ± 0.64) than adult (2.00 ± 0.13) arteries for 5-HT contractions. For both K + and 5-HT contractions, these relations were left shifted in fetal compared with adult arteries, indicating greater Ca 2+ sensitivity in fetal arteries. In contrast, slopes relating Ca 2+ i and %myosin phosphorylation for K + contractions were less in fetal (0.37 ± 0.08) than adult (0.81 ± 0.07) arteries, and the fetal curves were right shifted. For 5-HT contractions, the slope of the Ca 2+ -phosphorylation relation was similar in fetal (0.33 ± 0.09) and adult (0.33 ± 0.23) arteries, indicating that 5-HT depressed Ca 2+ -induced myosin phosphorylation in adult arteries. For slopes relating %myosin phosphorylation and tension, fetal values (K + : 1.52 ± 0.22, 5-HT: 7.66 ± 1.70) were less than adult values (K + : 2.13 ± 0.30, 5-HT: 8.29 ± 2.40) for both K + - and 5-HT-induced contractions, although again fetal curves were left shifted relative to the adult. Thus, in hypoxia-acclimatized basilar arteries, a downregulated ability of Ca 2+ to promote myosin phosphorylation is offset by an upregulated ability of phosphorylated myosin to produce force yielding an increased fetal myofilament Ca 2+ sensitivity. Postnatal maturation reprioritizes the mechanisms regulating hypoxic contractility through changes in the source of activator Ca 2+ , the pathways governing myosin light chain phosphorylation, and its interaction with actin. cerebral arteries; myofilament calcium sensitivity; postnatal maturation; myosin phosphorylation; thin filament regulation Address for reprint requests and other correspondence: W. J. Pearce, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350 (E-mail: wpearce@llu.edu ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Applied Physiology The American Physiological Society

Chronic hypoxia modulates relations among calcium, myosin light chain phosphorylation, and force differently in fetal and adult ovine basilar arteries

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References (43)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
8750-7587
eISSN
1522-1601
DOI
10.1152/japplphysiol.01131.2004
pmid
16036903
Publisher site
See Article on Publisher Site

Abstract

The present study tests the hypothesis that age-related differences in contractility of cerebral arteries from hypoxic animals involve changes in myofilament Ca 2+ sensitivity. Basilar arteries from term fetal and nonpregnant adult sheep maintained 110 days at 3,820 m were used in measurements of cytosolic calcium concentration (Ca 2+ i ), myosin light chain phosphorylation, and contractile tensions induced by graded concentrations of K + or serotonin (5-HT). Slopes relating Ca 2+ i to tension were similar in fetal (0.83 ± 0.07) and adult (1.02 ± 0.08) arteries for K + contractions but were significantly greater for fetal (3.77 ± 0.64) than adult (2.00 ± 0.13) arteries for 5-HT contractions. For both K + and 5-HT contractions, these relations were left shifted in fetal compared with adult arteries, indicating greater Ca 2+ sensitivity in fetal arteries. In contrast, slopes relating Ca 2+ i and %myosin phosphorylation for K + contractions were less in fetal (0.37 ± 0.08) than adult (0.81 ± 0.07) arteries, and the fetal curves were right shifted. For 5-HT contractions, the slope of the Ca 2+ -phosphorylation relation was similar in fetal (0.33 ± 0.09) and adult (0.33 ± 0.23) arteries, indicating that 5-HT depressed Ca 2+ -induced myosin phosphorylation in adult arteries. For slopes relating %myosin phosphorylation and tension, fetal values (K + : 1.52 ± 0.22, 5-HT: 7.66 ± 1.70) were less than adult values (K + : 2.13 ± 0.30, 5-HT: 8.29 ± 2.40) for both K + - and 5-HT-induced contractions, although again fetal curves were left shifted relative to the adult. Thus, in hypoxia-acclimatized basilar arteries, a downregulated ability of Ca 2+ to promote myosin phosphorylation is offset by an upregulated ability of phosphorylated myosin to produce force yielding an increased fetal myofilament Ca 2+ sensitivity. Postnatal maturation reprioritizes the mechanisms regulating hypoxic contractility through changes in the source of activator Ca 2+ , the pathways governing myosin light chain phosphorylation, and its interaction with actin. cerebral arteries; myofilament calcium sensitivity; postnatal maturation; myosin phosphorylation; thin filament regulation Address for reprint requests and other correspondence: W. J. Pearce, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350 (E-mail: wpearce@llu.edu )

Journal

Journal of Applied PhysiologyThe American Physiological Society

Published: Jul 1, 2005

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