Connexin-43 (Cx43) is a cardiac connexin involved with gap junction formation, the gap junctions facilitate the exchange of ions and metabolites between cytoplasm and extracellular milieu. Gap19, as selective connexin 43 (Cx43) hemichannel blocker, has cardioprotective properties.
CAT No: R0895
CAS No:1507930-57-5
Synonyms/Alias:Gap19;1507930-57-5;Gap19 TFA;(2S)-6-Amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-5-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]hexanoic acid;Gap19?;HY-P1136;C55H96N14O13;HB5162;AKOS025142096;DA-73656;CS-0028049;
In line with this, we found that Gap19 did not inhibit gap junction coupling in astrocytes as measured with dye transfer assays. At the same time, however, Gap19 strongly inhibited Cx43 hemichannels as exemplified by ATP release and dye uptake assays. Finally, we provide evidence that the TAT version of Gap19 is able to cross the intact blood-brain barrier indicating that this peptide can be used to block astroglial Cx43 hemichannel activity when applied through a vascular route.
The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
Gap 19 inhibits Cx43 hemichannels without blocking GJ channels or Cx40/pannexin-1 hemichannels. Hemichannel inhibition is due to the binding of Gap19 to the C-terminus (CT) thereby preventing intramolecular CT–CL interactions. The peptide inhibited Cx43 hemichannel unitary currents in both HeLa cells exogenously expressing Cx43 and acutely isolated pig ventricular cardiomyocytes. Treatment with Gap19 prevented metabolic inhibition-enhanced hemichannel openings, protected cardiomyocytes against volume overload and cell death following ischemia/reperfusion in vitro and modestly decreased the infarct size after myocardial ischemia/reperfusion in mice in vivo.
Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury
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