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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/L905    most recent 00053.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Goyal, R. Articles by Wilson, S. M. PubMed PubMed Citation Articles by Goyal, R. Articles by Wilson, S. M.

Maturation of intracellular calcium homeostasis in sheep pulmonary arterial smooth muscle cells

¹Department of Pharmacology, University of Mississippi School of Pharmacy and Research Institute of Pharmaceutical Sciences, and ²University of Mississippi Light Microscopy Core, University, Mississippi; ³Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California; and ⁴Department of Applied Science, College of William and Mary, Williamsburg, Virginia

Submitted 15 July 2008 ; accepted in final form 25 August 2008

Cytosolic Ca²⁺ signaling dynamics are important to pulmonary arterial reactivity, and alterations are implicated in pulmonary vascular disorders. Yet, adaptations in cellular Ca²⁺ homeostasis and receptor-mediated Ca²⁺ 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 Ca²⁺ homeostasis and receptor-generated Ca²⁺ 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 Ca²⁺ indicator fura 2. The results show that basal cytosolic and sarcoplasmic reticulum Ca²⁺ levels are attained before birth. Similarly, Ca²⁺ efflux pathways from the cytosol and basal as well as capacitative Ca²⁺ entry (CCE) are also developed before birth. However, receptor-mediated Ca²⁺ signaling adapts with maturation. Prominently, serotonin stimulation elicited Ca²⁺ elevations in very few fetal compared with adult PASMCs; in contrast, phenylephrine elevated Ca²⁺ in a similar percentage of fetal and adult PASMCs. Serotonin and phenylephrine elicited Ca²⁺ 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 Ca²⁺ in equivalent numbers of fetal and adult PASMCs. However, the caffeine-induced cytosolic Ca²⁺ 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 Ca²⁺ signaling, but not in cellular Ca²⁺ homeostasis.

fura 2; plasma membrane Ca²⁺-ATPase; sarco(endo)plasmic reticulum Ca²⁺-ATPase; capacitative Ca²⁺ entry; inositol trisphosphate; ryanodine receptor; ATP; serotonin; caffeine