| First Author | Miro-Casas E | Year | 2009 |
| Journal | Cardiovasc Res | Volume | 83 |
| Issue | 4 | Pages | 747-56 |
| PubMed ID | 19460776 | Mgi Jnum | J:167966 |
| Mgi Id | MGI:4881410 | Doi | 10.1093/cvr/cvp157 |
| Citation | Miro-Casas E, et al. (2009) Connexin43 in cardiomyocyte mitochondria contributes to mitochondrial potassium uptake. Cardiovasc Res 83(4):747-56 |
| abstractText | AIMS: Connexin43 is present at the inner membrane of cardiomyocyte mitochondria (mCx43), but its function remains unknown. METHODS AND RESULTS: 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dye uptake and K(+) flux was assessed in wild-type mice using hemichannel blockers and Cx43KI32 mice in which Cx43 had been replaced by Cx32.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 18alpha-glycyrrhetinic acid had an inhibitory effect on mitochondrial K(+) influx in wild-type cardiomyocytes, but not in cardiomyocytes from Cx32 mutants. CONCLUSION: These results indicate that mCx43 contributes to mitochondrial K(+) flux in cardiomyocytes, potentially by forming hemichannel-like structures. |
