Postnatal maturation modulates relationships among cytosolic Ca2+, myosin light chain phosphorylation, and contractile tone in ovine cerebral arteries

The present study tests the hypothesis that age-related changes in patterns of agonist-induced myofilament Ca2+ sensitization involve corresponding differences in the relative contributions of thick- and thin-filament regulation to overall myofilament Ca2+ sensitivity. Posterior communicating cerebral arteries from term fetal and nonpregnant adult sheep were used in measurements of cytosolic Ca2+, myosin light chain (MLC) phosphorylation, and contractile tensions induced by varying concentrations of K+ or serotonin [5-hydroxy-tryptamine (5-HT)]. The results were used to assess the relative contributions of the relationships between cytosolic Ca2+ and MLC phosphorylation (thick-filament reactivity), along with the relationships between MLC phosphorylation and contractile tension (thin-filament reactivity), to overall myofilament Ca2+ sensitivity. For K+-induced contractions, both fetal and adult arteries exhibited similar basal myofilament Ca2+ sensitivity. Despite this similarity, thick-filament reactivity was greater in fetal arteries, whereas thin-filament reactivity was greater in adult arteries. In contrast, 5-HT-induced contractions exhibited increased myofilament Ca2+ sensitivity compared with K+-induced contractions for both fetal and adult cerebral arteries, and the magnitude of this effect was greater in fetal compared with adult arteries. When interpreted together with our previous studies of 5-HT-induced myofilament Ca2+ sensitization, we attributed the present effects to agonist enhancement of thick-filament reactivity in fetal arteries mediated by G protein receptor activation of a PKC-independent but RhoA-dependent pathway. In adult arteries, agonist stimulation enhanced thin-filament reactivity was also probably mediated through G protein-coupled activation of RhoA-dependent and PKC-independent mechanisms. Overall, the present data demonstrate that agonist-enhanced myofilament Ca2+ sensitivity can be partitioned into separate thick- and thin-filament effects, the magnitudes of which are different between fetal and adult cerebral arteries.