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 Ca(2+) sensitization involve corresponding differences in the relative contributions of thick- and thin-filament regulation to overall myofilament Ca(2+) sensitivity. Posterior communicating cerebral arteries from term fetal and nonpregnant adult sheep were used in measurements of cytosolic Ca(2+), myosin light chain (MLC) phosphorylation, and contractile tensions induced by varying concentrations of K(+) or serotonin [5-hydroxytryptamine (5-HT)]. The results were used to assess the relative contributions of the relationships between cytosolic Ca(2+) and MLC phosphorylation (thick-filament reactivity), along with the relationships between MLC phosphorylation and contractile tension (thin-filament reactivity), to overall myofilament Ca(2+) sensitivity. For K(+)-induced contractions, both fetal and adult arteries exhibited similar basal myofilament Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) sensitivity can be partitioned into separate thick- and thin-filament effects, the magnitudes of which are different between fetal and adult cerebral arteries.
Department of Physiology and Pharmacology, Center for Perinatal Biology, Loma Linda University, School of Medicine, Loma Linda, California 92354, USA.
Renan J
RJ
Sandoval
Elisha R
ER
Injeti
William T
WT
Gerthoffer
William J
WJ
Pearce
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000098:blood supply; D006360:Heat-Shock Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep; D046509:Tissue Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D006360:Heat-Shock Proteins; D018994:Myosin Light Chains; D043562:Receptors, G-Protein-Coupled; D014662:Vasoconstrictor Agents; D012701:Serotonin; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase; D020742:rhoA GTP-Binding Protein; D011188:Potassium; D002118:Calcium