Exciting and not so exciting roles of pannexins

Abstract

It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself. Under pathological conditions such as ischemia, trauma, inflammation, epilepsy, extracellular ATP concentrations increases drastically but the consequences of this surge is still difficult to characterize due to its rapid metabolism in ADP and adenosine, the latter having inhibitory action on neuronal activity. For seizures, for instance, the excitatory effect of ATP on neuronal activity is mainly related to its action of P2X receptors, while the inhibitory effects are related to activation of P1, adenosine receptors. Here we provide a mini review on the properties of pannexins with a main focus on Panx1 and its involvement in seizure activity. Although there are only few studies implicating Panx1 in seizures, they are illustrative of the dual role that Panx1 has on neuronal excitability.

Cellular Environment Remodels the Genomic Fabrics of Functional Pathways in Astrocytes

“…Figure illustrates this finding by the changes in the coordinated expression of Gja1 and Panx1 (encoding the major gap junction channel-forming protein Cx43 and the ATP release channel protein Panx1) with actin-cytoskeleton ( Figure 8a) and circadian rhythm (Figure 8b) genes. Both Panx1 and Cx43 are well-documented for their important roles in brain physiopathology [56,57] through networking of astrocytes and oligodendrocytes-by way of paracrine and intercellular-channel mediated pathways, respectively. This analysis shows that the expression synergism of Panx1 with Fgf18, Itga2b and Pdgfd in isolated (control) astrocytes was reversed to an antagonistic coordination by the proximity of Oli-neu cells (in insert), while the antagonism of Gja1 with Pip4k2b was turned into synergism.…”

Pannexin-1 Deficiency Decreases Epileptic Activity in Mice

“…The pannexin-1 (Panx1) protein forms a transmembrane channel with a vital, yet unresolved, role in modulating cellular hyperexcitability [ 1 , 2 , 3 ]. As Panx1 is highly expressed in the post-synaptic compartment of hippocampal and cortical pyramidal neurons, it is in a prime position for interacting with the molecular, structural, ionic and electrical changes in the synaptic cleft during active communication.…”

Pannexin-1 channels contribute to seizure generation in human epileptic brain tissue and in a mouse model of epilepsy

“…Despite their modulated expression and activation under epileptiform conditions, the contribution of Panx1 to seizures during the course of chronic epilepsy in humans still remains unknown. Previous studies examining the impact of Panx1 on acute epileptiform activity induced either ex vivo or in vivo in mice reported controversial results (20,(23)(24)(25): Panx1 channels have been shown to contribute to status epilepticus in juvenile mice (13), in agreement with their ability to promote aberrant bursting activity after N-methyl-d-aspartate (NMDA) receptor activation in vitro (26), whereas they decreased susceptibility to acutely evoked seizures in adult mice in vivo via the P2X purinergic receptor 7 (P2X7)-Panx1 complex (27).…”