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

J. Biol. Chem., Vol. 278, Issue 7, 4875-4881, February 14, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/7/4875    most recent M209206200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, I. F. Articles by Peers, C. Search for Related Content PubMed PubMed Citation Articles by Smith, I. F. Articles by Peers, C. Social Bookmarking                      What's this?

Hypoxic Remodeling of Ca²⁺ Stores in Type I Cortical Astrocytes^*

Ian F. Smith, John P. Boyle, Leigh D. Plant, Hugh A. Pearson, and Chris Peers^§

From the Institute for Cardiovascular Research and the  School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom

Prolonged periods of hypoxia are deleterious to higher brain functions and increase the likelihood of developing dementias. Here, we have used fluorimetric techniques to investigate the effects of chronic hypoxia (2.5% O₂, 24 h) on Ca²⁺ stores in type I cortical astrocytes, because such stores are crucial to various astrocyte functions, including Ca²⁺-dependent modulation of neuronal activity. Rises of [Ca²⁺]_i evoked by exposure of astrocytes to bradykinin were enhanced following chronic hypoxia, as were transient increases in [Ca²⁺]_i recorded in Ca²⁺-free perfusate. The enhanced responses were due partly to impaired plasmalemmal Na⁺/Ca²⁺ exchange following chronic hypoxia. More importantly, chronic hypoxia increased the Ca²⁺ content of mitochondria (as determined by exposing cells to mitochondrial inhibitors), such that they were unable to act as Ca²⁺ buffers following bradykinin-evoked Ca²⁺ release from the endoplasmic reticulum. Hypoxic enhancement of mitochondrial Ca²⁺ content was also observed in confocal images of cells loaded with the mitochondrial Ca²⁺ indicator, Rhod-2. Confocal imaging of cells loaded with tetramethylrhodamine ethyl ester, an indicator of mitochondrial membrane potential, indicated that mitochondria were hyperpolarized in astrocytes following chronic hypoxia. Our findings indicate that hypoxia disturbs Ca²⁺ signaling in type I astrocytes, primarily by causing mitochondrial Ca²⁺ overload.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				B. Lenart, D. B. Kintner, G. E. Shull, and D. Sun Na-K-Cl Cotransporter-Mediated Intracellular Na+ Accumulation Affects Ca2+ Signaling in Astrocytes in an In Vitro Ischemic Model J. Neurosci., October 27, 2004; 24(43): 9585 - 9597. [Abstract] [Full Text] [PDF]