Gap19 is a selective inhibitor of connexin 43 (Cx43) hemichannel with IC50 value of ~ 50 μM [1].
Gap19 is identical to a short sequence present on the intracellular cytoplasmic loop domain of Cx43 hemichannel. It strongly inhibits Cx43 hemichannels which are involved in neuroglial interactions that participate to the control of neuronal activity and survival [2].
In cultured cortical astrocytes triggered by glutamate, pre-incubation of Gap19 for 30 min inhibited ATP release with IC50 values of 142 μM. At concentrations ranging from 0 μM to 688 μM, Gap19 inhibited astroglial Cx43 hemichannels in a dose-dependent manner, without affecting gap junction channels [2].
In a mouse model of middle cerebral artery occlusion, Gap19 (300 μg/kg, i.c.v.) significantly alleviated infarct volume, neuronal cell damage, as well as neurological deficits after ischemia. Moreover, post-treatment with TAT-Gap19 at the dose of 25 mg/kg still provided neuroprotection when it was administered intraperitoneally at 4 h after reperfusion [3].
References:
[1]. Iyyathurai J, D'hondt C, Wang N, et al. Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: gap junctions versus hemichannels. Neuropharmacology, 2013, 75: 491-505.
[2]. Abudara V, Bechberger J, Freitas-Andrade M, et al. The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes. Frontiers in Cellular Neuroscience, 2014, 8: 306.
[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 mice. Brain Research Bulletin, 2019, 146: 124-135.
