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- Title
Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca elevation.
- Authors
Wang, Nan; De Bock, Marijke; Antoons, Gudrun; Gadicherla, Ashish; Bol, Mélissa; Decrock, Elke; Evans, William; Sipido, Karin; Bukauskas, Feliksas; Leybaert, Luc
- Abstract
Connexin mimetic peptides (CxMPs), such as Gap26 and Gap27, are known as inhibitors of gap junction channels but evidence is accruing that these peptides also inhibit unapposed/non-junctional hemichannels (HCs) residing in the plasma membrane. We used voltage clamp studies to investigate the effect of Gap26/27 at the single channel level. Such an approach allows unequivocal identification of HC currents by their single channel conductance that is typically ~220 pS for Cx43. In HeLa cells stably transfected with Cx43 (HeLa-Cx43), Gap26/27 peptides inhibited Cx43 HC unitary currents over minutes and increased the voltage threshold for HC opening. By contrast, an elevation of intracellular calcium ([Ca]) to 200-500 nM potentiated the unitary HC current activity and lowered the voltage threshold for HC opening. Interestingly, Gap26/27 inhibited the Ca-potentiated HC currents and prevented lowering of the voltage threshold for HC opening. Experiments on isolated pig ventricular cardiomyocytes, which display strong endogenous Cx43 expression, demonstrated voltage-activated unitary currents with biophysical properties of Cx43 HCs that were inhibited by small interfering RNA targeting Cx43. As observed in HeLa-Cx43 cells, HC current activity in ventricular cardiomyocytes was potentiated by [Ca] elevation to 500 nM and was inhibited by Gap26/27. Our results indicate that under pathological conditions, when [Ca] is elevated, Cx43 HC opening is promoted in cardiomyocytes and CxMPs counteract this effect.
- Subjects
PEPTIDES; CONNEXINS; GAP junctions (Cell biology); CALCIUM channels; HELA cells; HEART cells; RNA; CELL membranes
- Publication
Basic Research in Cardiology, 2012, Vol 107, Issue 6, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-012-0304-2