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- Title
P117 Co-expressed cardiac connexins: dependence on the Cx43:Cx40 ratio in regulating the gap junction channel make-up and electrical properties.
- Authors
Chaigne, S; Dupuis, S; Constantin, M; Desplantez, T
- Abstract
Gap junction channels (GJC) ensure the direct electrical and chemical cell-to-cell communication. In the heart their biophysical electrical properties are considered as a key factor for regulating the impulse propagation through the cardiac network and ensuring the coordinated atrial and ventricular contractions. GJC are made of connexins Cx43, Cx40, Cx45 and Cx30.2 that display distinct specific expression patterns in the differentiated cardiac myocytes and conduction system. The connexins dysfunction and remodeling, i.e. altered expression and localization, are believed to be a major source of cardiac arrhythmias. The aim of this study is to investigate the distinct contribution of Cx40 and Cx43 in the GJC make-up and electrical properties in function of the healthy and diseased changes of levels of expression. Rat Liver Epithelial (RLE) cells that express Cx43 and stably transfected to co-express Cx40 at accurate Cx43:Cx40 ratios of 0.5, 1 and 2, are used. Dual voltage clamp recordings on cell pairs are performed to determine the electrical properties of GJC at each ratio. Compared to single Cx43 expression, we observed that a high ratio Cx43:Cx40 decreases the electrical coupling whereas lower Cx43:Cx40 ratio increase the coupling. Interestingly, induction of Cx40 expression decreases the voltage dependence and the kinetics of deactivation of GJC: the higher the induction of Cx40, the stronger the effects. Preliminary experiments that investigate the kinetics of recovery from deactivation show that Cx40 induction slows or accelerates the recovery in function of the level of induction and the Vj amplitude. Single channel recordings are under investigation to correlate the electrical properties to the GJC composition. Our results suggest a distinct GJC make-up, electrical properties and function that depends on the Cx43:Cx40 ratio. These findings will improve our understanding on the regulation of the gap junction channels make-up by Cx43 and Cx40, and how this is translated into specific conduction velocities of the cardiac impulse propagation in the healthy and diseased heart.
- Subjects
CONNEXINS; GAP junctions (Cell biology); HEART physiology; GENE expression; MUSCLE cells; COMPARATIVE studies
- Publication
Cardiovascular Research, 2014, Vol 103, Issue suppl_1, pS20
- ISSN
0008-6363
- Publication type
Academic Journal
- DOI
10.1093/cvr/cvu082.58