It has been suggested that these globins may enhance the flux of O2 to a terminal oxidase of the respiratory chain, especially under hypoxic conditions, or that they may protect the terminal oxidase from reactive oxygen or nitrogen species. Because there is no respiratory chain in the cell membrane of eukaryotes, any such role of GbX can be excluded. In addition, it has been proposed that some bacterial membrane-globins may preserve the integrity of membrane lipids by reducing peroxides that had been formed in response to ROS stress. Such a function is in fact conceivable for GbX. This may further explain the association of GbX with the sensory nerve system, which is known to have high metabolic rates and thus high ROS production. As Cys residues are a target for in vivo H2O2, this feature may link Cys redox state of GbX with yet unidentified heme reactivity in vivo. Alternatively, GbX may be involved in some type of R428 1037624-75-1 signal transduction process, either directly as an O2 sensor or as a binding partner in signal cascades. This hypothesis is in line with the acylation and membrane-association of GbX. GbX may act as O2-sensing protein, provided that a reducing system exists to maintain the protein in the ferrous form. Although several heme-containing proteins either of mitochondrial or nonmitochondrial origin have been described as putative O2 sensors, in most cases the signal transduction mechanism is unknown. In some prokaryotes, O2 is detected by globincoupled sensors which consist of a regulatory globin-like hemebinding domain and a linked transducer domain. Recently, is has been proposed that vertebrate Cygb oxidizes lipids, thereby generating signaling lipids under oxidative conditions. In analogy, a signaling function is also conceivable for GbX. Although additional studies clearly are required to elucidate the true physiological role of GbX, the identification of this acylated, membrane-bound globin adds a new and unexpected complexity to the family of vertebrate globins. The fact that GbX has been lost in “higher vertebrates” must be taken into account when explaining its function. Among the various types of paracrine signals, purinergic ATPmediated signaling is emerging as one of the most prominent form involved in neural cell interactions. This is because all neural cell types are able to release and respond to ATP and/or its metabolites. Purinergic signaling is not only involved in physiological glia-glia and glia-neuronal communication, but also plays critical roles in events related to epileptogenesis. Generalized seizures were reported after microinjection of ATP into the pre-piriform cortex and augmented levels of ATP were measured in hippocampi of mice with audiogenic seizures. Recently, Pannexin1 in pyramidal neurons was found to contribute to NMDA-mediated epileptiform activity by increasing spike amplitude and decreasing burst intervals. Pannexins are a group of proteins that share sequence homologies with the invertebrate gap junction proteins, the innexins.