title: Maturation of intracellular calcium homeostasis in sheep pulmonary arterial smooth muscle cells.
abstract: Cytosolic Ca(2+) signaling dynamics are important to pulmonary arterial reactivity, and alterations are implicated in pulmonary vascular disorders. Yet, adaptations in cellular Ca(2+) homeostasis and receptor-mediated Ca(2+) signaling with maturation from fetal to adult life in pulmonary arterial smooth muscle cells (PASMCs) are not known. The present study tested the hypothesis that cytosolic Ca(2+) homeostasis and receptor-generated Ca(2+) signaling adapt with maturation in sheep PASMCs. Digitalized fluorescence microscopy was performed using isolated PASMCs from fetal and adult sheep that were loaded with the Ca(2+) indicator fura 2. The results show that basal cytosolic and sarcoplasmic reticulum Ca(2+) levels are attained before birth. Similarly, Ca(2+) efflux pathways from the cytosol and basal as well as capacitative Ca(2+) entry (CCE) are also developed before birth. However, receptor-mediated Ca(2+) signaling adapts with maturation. Prominently, serotonin stimulation elicited Ca(2+) elevations in very few fetal compared with adult PASMCs; in contrast, phenylephrine elevated Ca(2+) in a similar percentage of fetal and adult PASMCs. Serotonin and phenylephrine elicited Ca(2+) increases of a similar magnitude in reactive cells of fetus and adult, supporting the assertion that inositol trisphosphate signaling is intact. Caffeine and ATP elevated Ca(2+) in equivalent numbers of fetal and adult PASMCs. However, the caffeine-induced cytosolic Ca(2+) increase was significantly greater in fetal PASMCs, whereas the ATP-elicited increase was greater in adult cells. Overall, the results of this study demonstrate selective adaptations in receptor-mediated Ca(2+) signaling, but not in cellular Ca(2+) homeostasis.
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Goyal
authors.forename: Kara D
authors.initials: KD
authors.lastname: Creel
authors.forename: Erica
authors.initials: E
authors.lastname: Chavis
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Smith
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D006706:Homeostasis / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep
chemical_list: D011942:Receptors, Adrenergic, alpha; D018048:Receptors, Purinergic P2; D012701:Serotonin; D002110:Caffeine; D002118:Calcium
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