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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/L1007    most recent 00171.2007v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Yang, M. Articles by Murray, P. A. Search for Related Content PubMed PubMed Citation Articles by Yang, M. Articles by Murray, P. A.

Differential effects of intravenous anesthetics on capacitative calcium entry in human pulmonary artery smooth muscle cells

Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, Ohio; and Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Submitted 27 April 2007 ; accepted in final form 12 March 2008

We assessed the roles of the protein kinase C (PKC) and the tyrosine kinase (TK) signaling pathways in regulating capacitative calcium entry (CCE) in human pulmonary artery smooth muscle cells (PASMCs) and investigated the effects of intravenous anesthetics (midazolam, propofol, thiopental, ketamine, etomidate, morphine, and fentanyl) on CCE in human PASMCs. Fura-2-loaded human PASMCs were placed in a dish (37°C) on an inverted fluorescence microscope. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured as the 340/380 fluorescence ratio in individual PASMCs. Thapsigargin, a sarcoplasmic reticulum Ca²⁺-adenosine triphosphatase inhibitor, was used to deplete intracellular Ca²⁺ stores after removing extracellular Ca²⁺. CCE was then activated by restoring extracellular Ca²⁺ (2.2 mM). The effects of PKC activation and inhibition, TK inhibition, and the intravenous anesthetics on CCE were assessed. Thapsigargin caused a transient increase in [Ca²⁺]_i. Restoring extracellular Ca²⁺ caused a rapid peak increase in [Ca²⁺]_i, followed by a sustained increase in [Ca²⁺]_i; i.e., CCE was stimulated in human PASMCs. PKC activation attenuated (P < 0.05), whereas PKC inhibition potentiated (P < 0.05), both peak and sustained CCE. TK inhibition attenuated (P < 0.05) both peak and sustained CCE. Midazolam, propofol, and thiopental each attenuated (P < 0.05) both peak and sustained CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE. Our results suggest that CCE in human PASMCs is influenced by both the TK and PKC signaling pathways. Midazolam, propofol, and thiopental each attenuated CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE.

protein kinase C; tyrosine kinase