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PMID: 15272030 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Role of ATP-conductive anion channel in ATP release from neonatal rat cardiomyocytes in ischaemic or hypoxic conditions.

The Journal of physiology ·Vol. 559 ·No. Pt 3 ·2004-09-15 ·Pages 799-812

Dutta AK, Sabirov RZ, Uramoto H, Okada Y

Abstract

It is known that the level of ATP in the interstitial spaces within the heart during ischaemia or hypoxia is elevated due to its release from a number of cell types, including cardiomyocytes. However, the mechanism by which ATP is released from these myocytes is not known. In this study, we examined a possible involvement of the ATP-conductive maxi-anion channel in ATP release from neonatal rat cardiomyocytes in primary culture upon ischaemic, hypoxic or hypotonic stimulation. Using a luciferin-luciferase assay, it was found that ATP was released into the bulk solution when the cells were subjected to chemical ischaemia, hypoxia or hypotonic stress. The swelling-induced ATP release was inhibited by the carboxylate- and stilbene-derivative anion channel blockers, arachidonic acid and Gd3+, but not by glibenclamide. The local concentration of ATP released near the cell surface of a single cardiomyocyte, measured by a biosensor technique, was found to exceed the micromolar level. Patch-clamp studies showed that ischaemia, hypoxia or hypotonic stimulation induced the activation of single-channel events with a large unitary conductance (approximately 390 pS). The channel was selective to anions and showed significant permeability to ATP4- (PATP/PCl approximately 0.1) and MgATP2- (PATP/PCl approximately 0.16). The channel activity exhibited pharmacological properties essentially identical to those of ATP release. These results indicate that neonatal rat cardiomyocytes respond to ischaemia, hypoxia or hypotonic stimulation with ATP release via maxi-anion channels.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Animals, Newborn Cell Hypoxia/drug effects,physiology Cells, Cultured Hypotonic Solutions/pharmacology Ion Channels/metabolism Myocytes, Cardiac/drug effects,metabolism Osmotic Pressure/drug effects PC12 Cells Rats Rats, Wistar
Chemicals
Hypotonic Solutions Ion Channels Adenosine Triphosphate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dutta Amal K
Department of Cell Physiology, National Institute for Physiological Sciences, Myodaiji-cho, Okazaki 444-8585, Japan.
Sabirov Ravshan Z
Uramoto Hiromi
Okada Yasunobu
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
Published
2004-09-15
Epub
2004-00-22
Pages
799-812
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1665184
Subset
IM
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