HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/5/L917    most recent 00403.2004v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Keck, M. Articles by Cornfield, D. N. Search for Related Content PubMed PubMed Citation Articles by Keck, M. Articles by Cornfield, D. N.

Oxygen increases ductus arteriosus smooth muscle cytosolic calcium via release of calcium from inositol triphosphate-sensitive stores

Division of Pediatric Pulmonary and Critical Care Medicine, Departments of ¹Pediatrics, ²Physiology, and ³Surgery, University of Minnesota, Minneapolis, Minnesota

Submitted 29 October 2004 ; accepted in final form 4 January 2005

In utero, blood shunts away from the lungs via the ductus arteriosus (DA) and the foramen ovale. After birth, the DA closes concomitant with increased oxygen tension. The present experimental series tests the hypothesis that oxygen directly increases DA smooth muscle cell (SMC) cytosolic calcium ([Ca²⁺]_i) through inactivation of a K⁺ channel, membrane depolarization, and entry of extracellular calcium. To test the hypothesis, DA SMC were isolated from late-gestation fetal lambs and grown to subconfluence in primary culture in low oxygen tension (25 Torr). DA SMC were loaded with the calcium-sensitive fluorophore fura-2 under low oxygen tension conditions and studied using microfluorimetry while oxygen tension was acutely increased (120 Torr). An acute increase in oxygen tension progressively increased DA SMC [Ca²⁺]_i by 11.7 ± 1.4% over 40 min. The effect of acute normoxia on DA SMC [Ca²⁺]_i was mimicked by pharmacological blockade of the voltage-sensitive K⁺ channel. Neither removal of extracellular calcium nor voltage-operated calcium channel blockade prevented the initial increase in DA SMC [Ca²⁺]_i. Manganese quenching experiments demonstrated that acute normoxia initially decreases the rate of extracellular calcium entry. Pharmacological blockade of inositol triphosphate-sensitive, but not ryanodine-sensitive, intracellular calcium stores prevented the oxygen-induced increase in [Ca²⁺]_i. Endothelin increased [Ca²⁺]_i in acutely normoxic, but not hypoxic, DA SMC. Thus acute normoxia 1) increases DA SMC [Ca²⁺]_i via release of calcium from intracellular calcium stores, and subsequent entry of extracellular calcium, and 2) potentiates the effect of contractile agonists. Prolonged patency of the DA may result from disordered intracellular calcium homeostasis.

oxygen sensing; pulmonary hypertension potassium channels; vascular biology

This article has been cited by other articles:

				H. Kajimoto, K. Hashimoto, S. N. Bonnet, A. Haromy, G. Harry, R. Moudgil, T. Nakanishi, I. Rebeyka, B. Thebaud, E. D. Michelakis, et al. Oxygen Activates the Rho/Rho-Kinase Pathway and Induces RhoB and ROCK-1 Expression in Human and Rabbit Ductus Arteriosus by Increasing Mitochondria-Derived Reactive Oxygen Species: A Newly Recognized Mechanism for Sustaining Ductal Constriction Circulation, April 3, 2007; 115(13): 1777 - 1788. [Abstract] [Full Text] [PDF]

				Z. Hong, F. Hong, A. Olschewski, J. A. Cabrera, A. Varghese, D. P. Nelson, and E. K. Weir Role of Store-Operated Calcium Channels and Calcium Sensitization in Normoxic Contraction of the Ductus Arteriosus Circulation, September 26, 2006; 114(13): 1372 - 1379. [Abstract] [Full Text] [PDF]

				M. Costa, S. Barogi, N. D. Socci, D. Angeloni, M. Maffei, B. Baragatti, C. Chiellini, E. Grasso, and F. Coceani Gene expression in ductus arteriosus and aorta: comparison of birth and oxygen effects Physiol Genomics, April 13, 2006; 25(2): 250 - 262. [Abstract] [Full Text] [PDF]