Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wang, N; De Bock, M; Antoons, G; Gadicherla, AK; Bol, M; Decrock, E; Evans, WH; Sipido, KR; Bukauskas, FF; Leybaert, L; .
Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+ elevation.
Basic Res Cardiol. 2012; 107(6):304-304
Doi: 10.1007/s00395-012-0304-2
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- 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(2+)](i)) to 200-500 nM potentiated the unitary HC current activity and lowered the voltage threshold for HC opening. Interestingly, Gap26/27 inhibited the Ca(2+)-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(2+)](i) elevation to 500 nM and was inhibited by Gap26/27. Our results indicate that under pathological conditions, when [Ca(2+)](i) is elevated, Cx43 HC opening is promoted in cardiomyocytes and CxMPs counteract this effect.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium - metabolism
- Connexin 43 - metabolism
- HeLa Cells -
- Humans -
- Ion Channels - metabolism
- Membrane Potentials -
- Myocytes, Cardiac - metabolism
- Patch-Clamp Techniques -
- Peptides -
- Swine -
- Find related publications in this database (Keywords)
- Connexin 43
- Connexin hemichannel
- Mimetic peptides
- Cardiomyocytes
- Single channel