Connexins and pannexins: At the junction of neuro‐glial homeostasis & disease
Accruing evidence indicates that connexin (Cx) and pannexin (Panx) transmembrane channels are crucial for the coordination and maintenance of physiologic CNS activity. In neurons, Cxs electrochemically couple neurons by electrical synapses (Galarreta & Hestrin, 1999), while glial Cxs mediate numerous functions ranging from K+ buffering to direct modulation of glutamatergic activity (Battefeld, Klooster, & Kole, 2016; Chever, Lee, & Rouach, 2014a; Kamasawa et al., 2005; Kofuji & Newman, 2004). Alone, Cxs and Panxs represent a mechanism for robust autocrine and paracrine signaling through gliotransmitter release, which are essential to synaptic strength and plasticity (Prochnow et al., 2012; Thompson et al., 2008). Dysregulation of Cx and Panx activity is implicated in neurodegenerative disease (Markoullis et al., 2012a) and may be etiologic in some human epilepsy (Bedner et al., 2015). In addition, Cx and Panx sensitivity to inflammatory mediators suggests that neuronal excitability may be altered in a range of disease states. In the following sections, we will describe the structure, function, regulation, and distribution of CNS Cx and Panx molecules. We will also summarize evidence for their functions related to neuronal excitability under homeostatic conditions and examine their role as effectors of pathological glutamatergic transmission.