Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 99, Issue 1, Pages 120-127Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.01131.2004
Keywords
cerebral arteries; myofilament calcium sensitivity; postnatal maturation; myosin phosphorylation; thin filament regulation
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Funding
- NHLBI NIH HHS [HL-064867, HL-54120] Funding Source: Medline
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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.
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