Abstract
In the brain, astrocytes represent the cellular population that expresses the highest amount of connexins (Cxs). This family of membrane proteins is the molecular constituent of gap junction channels and hemichannels that provide pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, respectively. Both types of Cx channels are permeable to ions and small signaling molecules allowing astrocytes to establish dynamic interactions with neurons. So far, most pharmacological approaches currently available do not distinguish between these two channel functions, stressing the need to develop new specific molecular tools. In astrocytes two major Cxs are expressed, Cx43 and Cx30, and there is now evidence indicating that at least Cx43 operates as a gap junction channel as well as a hemichannel in these cells. Based on studies in primary cultures as well as in acute hippocampal slices, we report here that Gap19, a nonapeptide derived from the cytoplasmic loop of Cx43, inhibits astroglial Cx43 hemichannels in a dose-dependent manner, without affecting gap junction channels. This peptide, which not only selectively inhibits hemichannels but is also specific for Cx43, can be delivered in vivo in mice as TAT-Gap19, and displays penetration into the brain parenchyma. As a result, Gap19 combined with other tools opens up new avenues to decipher the role of Cx43 hemichannels in interactions between astrocytes and neurons in physiological as well as pathological situations.
Highlights
Compared to neurons, astrocytes make up the brain cell population that expresses the highest amount of the gap junction proteins, named connexins (Cxs) (Ransom and Giaume, 2013)
To determine whether these findings apply for brain cells, especially astrocytes which predominantly express Cx43 (Ransom and Giaume, 2013), we tested the effect of this peptide on hemichannel activity (Etd+ uptake and ATP release assays) and gap junctional communication in two in vitro preparations: primary cultures of astrocytes and acute hippocampal slices
Since in confluent cultures of astrocytes intercellular communication through Cx43 gap junction channels is high (Giaume et al, 1991b), we tested whether Gap19 (344 μM and 688 μM 30 min) had any effect on the level of gap junctional coupling
Summary
Astrocytes make up the brain cell population that expresses the highest amount of the gap junction proteins, named connexins (Cxs) (Ransom and Giaume, 2013). The exclusive use of such animals does not distinguish between the contributions of the two types of astroglial Cxs as well as between the channel and hemichannel functions that they support (Giaume and Theis, 2010). The use of single Cx knock-out mice has provided key data demonstrating a role of Cx43 in neuronal migration (Elias et al, 2007; Cina et al, 2009), a synaptic activitydependent modulation of Cx30 gap junctions in astrocytes in the olfactory bulb (Roux et al, 2011) and recently, it was reported that the lack of Cx30 impacts synaptic transmission through the modulation of astroglial glutamate transport (Pannasch et al, 2014). There is still a need to develop new pharmacological tools to design in vitro and in vivo experiments studying the role of Cxs in astrocytes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
