期刊
CARDIOVASCULAR RESEARCH
卷 83, 期 4, 页码 747-756出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvp157
关键词
Connexins; Hemichannels; Myocardial ischaemia; Preconditioning; Reperfusion
资金
- Spanish Ministry of Health-RETICS (RECAVA) [FIS-PI060996]
- CICYT [SAF2005-01758]
- Generalitat de Catalunya
- German Research Foundation (DFG ) [Schulz 843/7-1, Schu 843/7-2]
Connexin43 is present at the inner membrane of cardiomyocyte mitochondria (mCx43), but its function remains unknown. In this study we verified the presence of mCx43 by a mass spectrometry-based proteomic approach in purified mitochondrial preparations from mouse myocardium and determined by western blot analysis that the C-terminus of mCx43 is oriented towards the intermembrane space. Cross-linking studies with dimethylsuberimidate indicated the presence of Cx43 hexamers in mitochondrial membranes. The contribution of Cx43 to both mitochondrial dye uptake and K+ flux was assessed in wild-type mice using hemichannel blockers and Cx43KI32 mice in which Cx43 had been replaced by Cx32. Uptake of the Cx43 hemichannel-permeant dye Lucifer Yellow was reduced in mitochondria from wild-type mice by two hemichannel blockers (carbenoxolone and heptanol) and in Cx43KI32 compared with wild-type mice. Mitochondrial K+ influx (PBFI fluorescence) was decreased in digitonin-permeabilized cardiomyocytes from Cx32 mutants compared with wild-type mice, and addition of the Cx43 hemichannel blocker 18 alpha-glycyrrhetinic acid had an inhibitory effect on mitochondrial K+ influx in wild-type cardiomyocytes, but not in cardiomyocytes from Cx32 mutants. These results indicate that mCx43 contributes to mitochondrial K+ flux in cardiomyocytes, potentially by forming hemichannel-like structures.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据