Journal of Applied Physiology Journal of Applied Physiology
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J Appl Physiol 99: 120-127, 2005; doi:10.1152/japplphysiol.01131.2004
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Chronic hypoxia modulates relations among calcium, myosin light chain phosphorylation, and force differently in fetal and adult ovine basilar arteries

Surya M. Nauli,1 James M. Williams,2 William T. Gerthoffer,3 and William J. Pearce2

1Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; 2Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and 3Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada

Submitted 7 October 2004 ; accepted in final form 5 March 2005

The present study tests the hypothesis that age-related differences in contractility of cerebral arteries from hypoxic animals involve changes in myofilament Ca2+ 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 ([Ca2+]i), myosin light chain phosphorylation, and contractile tensions induced by graded concentrations of K+ or serotonin (5-HT). Slopes relating [Ca2+]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 Ca2+ sensitivity in fetal arteries. In contrast, slopes relating [Ca2+]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 Ca2+-phosphorylation relation was similar in fetal (0.33 ± 0.09) and adult (0.33 ± 0.23) arteries, indicating that 5-HT depressed Ca2+-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 Ca2+ to promote myosin phosphorylation is offset by an upregulated ability of phosphorylated myosin to produce force yielding an increased fetal myofilament Ca2+ sensitivity. Postnatal maturation reprioritizes the mechanisms regulating hypoxic contractility through changes in the source of activator Ca2+, 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{at}llu.edu)




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