Submitted on June 5, 2007
Accepted on July 26, 2007
POSTNATAL MATURATION MODULATES RELATIONS AMONG CYTOSOLIC CA2+, MYOSIN LIGHT CHAIN PHOSPHORYLATION, AND CONTRACTILE TONE IN OVINE CEREBRAL ARTERIES
Renan Joel Sandoval1, Elisha Raju Injetti1, William T. Gerthoffer2, and William J Pearce3*
1 Center for Perinatal Biology, Loma Linda University, Loma Linda, California, United States
2 Department of Pharmacology, University of Nevada at Reno, Reno, Nevada, United States
3 Center for Perinatal Biology, Loma Linda University, Loma Linda, California, United States; Physiology, Loma Linda University, School of Medicine, Loma Linda, California, 92350, United States
* To whom correspondence should be addressed. E-mail: wpearce{at}llu.edu.
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-filament and thin-filament regulation to overall myofilament Ca2+ sensitivity. Posterior communicating cerebral arteries from term fetal and non-pregnant adult sheep were used in the measurements of cytosolic Ca2+, myosin light chain phosphorylation, and contractile tensions induced by varying concentrations of K+ or serotonin (5-HT). The results were used to assess the relative contributions of the relations between cytosolic Ca2+ and MLC phosphorylation (thick-filament reactivity) along with the relations 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 to K+-induced contractions for both fetal and adult cerebral arteries, and the magnitude of this effect was greater in fetal compared to 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 rho-A dependent pathway. In adult arteries, agonist stimulation enhanced thin-filament reactivity that was also mediated thru G-protein coupled activation of rho-A dependent and PKC independent mechanisms. Overall, the present data demonstrate that agonist-enhanced myofilament Ca2+ sensitivity can be partitioned into separate thick-filament and thin-filament effects whose magnitudes are different between fetal and adult cerebral arteries.
