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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/H2289    most recent 00606.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Injeti, E. R. Articles by Pearce, W. J. Search for Related Content PubMed PubMed Citation Articles by Injeti, E. R. Articles by Pearce, W. J.

Maximal stimulation-induced in situ myosin light chain kinase activity is upregulated in fetal compared with adult ovine carotid arteries

¹Divisions of Physiology and Pharmacology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and ²Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 9 June 2008 ; accepted in final form 1 October 2008

Postnatal decreases in vascular reactivity involve decreases in the thick filament component of myofilament calcium sensitivity, which is measured as the relationship between cytosolic calcium concentration and myosin light chain (MLC₂₀) phosphorylation. The present study tests the hypothesis that downregulation of thick filament reactivity is due to downregulation of myosin light chain kinase (MLCK) activity in adult compared with fetal arteries. Total MLCK activity, calculated as %MLC₂₀ phosphorylated per second in intact arteries during optimal inhibition of myosin light chain phosphatase activity, was significantly less in adult (6.56 ± 0.29%) than in fetal preparations (7.39 ± 0.53%). In situ MLC₂₀ concentrations (µM) in adult (198 ± 28) and fetal arteries (236 ± 44) did not differ significantly. In situ MLCK concentrations (µM), however, were significantly greater in adult (8.21 ± 0.59) than in fetal arteries (1.83 ± 0.13). In situ MLCK activities (ng MLC₂₀ phosphorylated·s^–1·ng MLCK^–1) were significantly less in adult (0.26 ± 0.01) than in fetal arteries (1.52 ± 0.11). In contrast, MLCK activities in adult (15.8 ± 1.5) and fetal artery homogenates (17.3 ± 1.3) were not significantly different. When in situ fractional activation was calculated, adult values (1.72 ± 0.17%) were significantly less than fetal values (9.08 ± 0.83%). Together, these results indicate that decreased thick filament reactivity in adult compared with fetal ovine carotid arteries is due at least in part to greater MLCK activity in fetal arteries, which in turn cannot be explained by differences in MLCK, MLC₂₀, or calmodulin concentrations. Instead, this difference appears to involve age-related differences in fractional activation of the MLCK enzyme.

myofilament calcium sensitivity; postnatal maturation; regulatory myosin light chain; thick filament reactivity