A characteristic feature of astrocytes is their high level of intercellular communication mediated by connexin (Cx) channels, i.e. gap junction channels (GJs) connecting the cytoplasm of adjacent cells and hemichannels (hemi-GJs; HCs) forming a paracrine conduit between the cytoplasm and the extracellular environment. This type of network organization is not only of major importance for their neuronal supportive function but may have detrimental consequences as well, contributing to exacerbation of injury. The present study was set up to determine the contribution of both Cx channels in the communication of apoptosis towards surrounding cells.

We used an in situ electroporation technique to load a localized area of an adherent C6 glioma cell culture, stably transfected with Cx43 (C6Cx43), with the apoptotic agent Cytochrome C (CytC) and found that healthy surrounding cells underwent apoptotic transformation. Further work with wild type cells, inhibitors of GJs and/or HCs and Cx43 gene silencing showed that GJs contribute to the spread of apoptosis in a zone next to where apoptosis was triggered while HCs also promoted cell death beyond this area. Application of the calcium chelator BAPTA-AM and an inositol trisphosphate (IP₃) degrading phosphatase reduced the cell death mediated by GJs as well as HCs, suggesting that calcium and IP₃ are involved in both processes.

We conclude that Cx43 HCs can function as an entry route or a leakage pore for pro-apoptotic messengers, thereby playing a role in communicating cell death messages in concert with their GJ counterparts.