Maturational differences in the contributions of thick‐ and thin‐filament reactivity to myofilament Ca ++ sensitivity in ovine cerebral arteries

Abstract

The present study tests the hypothesis that the contributions of thick-filament and thin-filament reactivity to myofilament Ca++ sensitivity vary with postnatal age. K+-induced changes in cytosolic [Ca++], myosin light chain phosphorylation, and contractile tension were compared between posterior communicating arteries taken from term fetal and non-pregnant adult sheep. Across graded concentrations of K+, relations between [Ca++] and contractile tension were similar in fetal and adult arteries, indicating that basal Ca++ sensitivity changed little with age. However, K+-induced increases in MLC phosphorylation were greater in fetal (194±17 %phosphorylation-sec @ 71% Ca++ max) than adult (70±7 %phosphorylation-sec @ 64% Ca++ max) arteries, suggesting increased thick-filament reactivity in the fetus. In contrast, when contractile force was plotted against the corresponding extent of MLC phosphorylation to estimate thin filament reactivity, adult arteries exhibited much greater contractile tension at lower levels of MLC phosphorylation (66±6 %Kmax @ 70 %phosphorylation-sec) than observed in the fetal arteries (45±5 %Kmax @ 194 %phosphorylation-sec). This latter result demonstrates that thin-filament reactivity was depressed in fetal compared to adult cerebral arteries. Together, these results indicate that basal myofilament Ca++ sensitivity is regulated to a similar value in fetal and adult arteries, but that in fetal arteries thick-filament reactivity is upregulated and thin-filament reactivity is down-regulated, compared to the adult. Supported by NIH HD31226, HL54120, and HL64867.