Gap19 is a nonapeptide derivative of connexin43 (Cx43) and an inhibitor of Cx43 hemichannels.1,2 It suppresses the membrane charge transfer (Qm) in HeLa cells expressing Cx43 (IC50 = ~6.5 µM), as well as Cx43 hemichannel currents in isolated guinea pig cardiomyocytes when used at a concentration of 100 µM.1 Gap19 inhibits glutamate-induced ATP release, a marker of Cx43 hemichannel activity, in primary mouse astrocytes.2 In vivo, Gap19 (300 µg/kg, i.c.v.) decreases cortical neuronal loss, infarct volume, and the number of errors in a foot fault test in a mouse model of cerebral ischemia and reperfusion injury induced by middle cerebral artery occlusion (MCAO).3 It also reduces infarct size in a mouse model of myocardial ischemia and reperfusion injury induced by ligation of the left anterior descending (LAD) artery when administered at a dose of 25 mg/kg.1
1.Wang, N., De Vuyst, E., Ponsaerts, R., et al.Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injuryBasic Res. Cardiol.108(1)309(2013) 2.Abudara, V., Bechberger, J., Freitas-Andrade, M., et al.The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytesFront. Cell Neurosci.8306(2014) 3.Chen, B., Yang, L., Chen, J., et al.Inhibition of Connexin43 hemichannels with Gap19 protects cerebral ischemia/reperfusion injury via the JAK2/STAT3 pathway in miceBrain Res. Bull.146124-135(2019)