Skip Navigation

Cardiovascular Research 2000 47(2):394-403; doi:10.1016/S0008-6363(00)00108-5
© 2000 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Ladilov, Y.
Right arrow Articles by Piper, H.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ladilov, Y.
Right arrow Articles by Piper, H.M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2000, European Society of Cardiology

Mechanism of Ca2+ overload in endothelial cells exposed to simulated ischemia

Yury Ladilov*, Claudia Schäfer, Alexander Held, Matthias Schäfer, Thomas Noll and H.Michael Piper

Physiologisches Institut, Justus-Liebig-Universität, Aulweg 129, D-35392 Giessen, Germany

* Corresponding author. Tel.: +49-641-9947-215; fax: +49-641-9947-239 yury.ladilov{at}physiologie.med.uni-giessen.de

Objective: Several studies have shown that myocardial ischemia leads to functional failure of endothelial cells (EC) whereby disturbance of Ca2+ homeostasis may play an important role. The mechanisms leading to Ca2+ disbalance in ischemic EC are not fully understood. The aim of this study was to test effects of different components of simulated ischemia (glucose deprivation, anoxia, low extracellular pH (pHo) and lactate) on Ca2+ homeostasis in EC. Methods: Cytosolic Ca2+ (Cai), cytosolic pH (pHi) and ATP content were measured in cultured rat coronary EC. Results: In normoxic cells 60 min glucose deprivation at pHo 7.4 had no effect on pHi. It only slightly increased Cai and decreased ATP content. Reduction of pHo to 6.5 under these conditions led to marked cytosolic acidosis and Cai overload, but had no effect on ATP content. Anoxia at pHo 6.5 had no additional effect on Cai overload, but significantly reduced cellular ATP. Addition of 20 mmol/l lactate to anoxia at pHo 6.5 accelerated Cai overload due to faster cytosolic acidification. Acidosis-induced Cai overload was prevented by inhibition of Ca2+ release channels of endoplasmic reticulum (ER) with 3 µmol/l ryanodine or by pre-emptying the ER with thapsigargin. Re-normalisation of pHo for 30 min led to recovery of pHi, but not of Cai. Conclusion: The ischemic factors leading to cytosolic acidosis (low pHo and lactate) cause Cai overload in endothelial cells, while anoxia and glucose deprivation play only a minor role. The ER is the main source for this Cai rise. Cai overload is not readily reversible.

KEYWORDS Acidosis; Ca-channel; Calcium (cellular); Endothelial function; Ischemia; Reperfusion


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.