RRC ID 42199
著者 Dutta AK, Sabirov RZ, Uramoto H, Okada Y.
タイトル Role of ATP-conductive anion channel in ATP release from neonatal rat cardiomyocytes in ischaemic or hypoxic conditions.
ジャーナル J Physiol
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.
巻・号 559(Pt 3)
ページ 799-812
公開日 2004-9-15
DOI 10.1113/jphysiol.2004.069245
PII jphysiol.2004.069245
PMID 15272030
PMC PMC1665184
MeSH Adenosine Triphosphate / metabolism* Animals Animals, Newborn Cell Hypoxia / drug effects Cell Hypoxia / physiology Cells, Cultured Hypotonic Solutions / pharmacology Ion Channels / metabolism* Myocytes, Cardiac / drug effects Myocytes, Cardiac / metabolism* Osmotic Pressure / drug effects PC12 Cells Rats Rats, Wistar
IF 4.547
引用数 98
WOS 分野 PHYSIOLOGY NEUROSCIENCES
リソース情報
ヒト・動物細胞 PC-12(RCB0009)