Lar Ca2+ store-dependent mechanisms (F2) (Jeftinija and Jeftinija, 1998). ATP and excitatory amino acids can reciprocally bind to ionotropic and metabotropic Glu-, and P2X-receptors on unmyelinated peripheral axons and influence their excitability (F3) (Agrawal and Evans, 1986; Kinkelin et al., 2000; Carlton et al., 2001; Irnich et al., 2001). (G) Regulation of SC fate by neuronal activity by means of activation of ion channels (G1) (Wilson and Chiu, 1993; Pappas and Ritchie, 1998; Sobko et al., 1998), purinergic metabotropic P2Y1 receptors and A2A GPCRs by ATP and its metabolite adenosine (G2) (Stevens and Fields, 2000; Stevens et al., 2004; Fields and Burnstock, 2006), and of mGluRs (G3) (Saitoh and Araki, 2010). (H) Neurotrophic axonal support by SCs. (I) Vesicular transfer of molecules from SCs to axons. Exosomes, which are enclosed in multivesicular bodies (MVB), move from mSCs to axons by means of cytoplasmic-rich regions just like the SLIs and paranodal domains (I1), or may be released from dedifferentiatediSCs close to neuronal growth cones following injury (I2) (Ach Inhibitors products Lopez-Verrilli and Court, 2012). Shedding vesicles (SVs) are straight generated from SC plasma membrane evaginations typically in microvilli and paranodal regions of mSCs, and may fuse or be endocytosed by axons (I3) (Court et al., 2008; Cocucci et al., 2009; Lopez-Verrilli and Court, 2012). (J) Possible direct transfer route of SC molecules via GJs. Abbreviations: CaV , voltage-gated Ca2+ channel; ClV , voltage-gated Cl- channel; KV , voltage-gated K+ channel; Kir, inwardly rectifying K+ channel, NaV , voltage-gated Na+ channel; CFTR, Cystic Fibrosis Transmembrane conductance Regulator; VAAC, Volume-Activated Anion Channel; A2R, adenosine receptor 2; P2X and P2Y, purinergic receptor; iGluR, ionotropic glutamate receptor; mGluR, metabotropic glutamate receptor; GPCR, G-protein coupled receptor; NGF nerve growth factor; ER, Endoplasmic , Reticulum.Frontiers in Cellular Neurosciencewww.frontiersin.orgNovember 2013 | Volume 7 | Report 228 |Samara et al.PNS glia-neuron communicationadhesion molecules is under regulation by ES inside a pattern-specific manner (Itoh et al., 1997).DETECTION OF AXONAL SIGNALS BY SC ACTIVITY SENSORSSC responses to neuronal activity were initially recorded around the squid giant axon by electrophysiology (Evans et al., 1991). ES of axons or perfusion of neurotransmitters induced SC membrane hyperpolarization (Evans et al., 1991). Equivalent responses have been also reported in vertebrates, primarily inside the kind of SC Ca2+ transients that create subsequently to ES of myelinated and unmyelinated fibers (Figures 1D1,D2)(Brunet and Jirounek, 1994; Lev-Ram and Ellisman, 1995; Mayer et al., 1999). mSCs and nmSCs express molecules, which let them to respond to electrical or chemical axonal stimuli (Figure 1). SC “activity sensors,” such as voltage- and ligand-gated ion channels, transporters, pumps, G-protein coupled receptors (GPCRs), connexins (Cx) of hemichannels and GJs, happen to be detected at mRNA and protein levels in vivo (animal tissues or human biopsies), ex vivo (nerve preparations) andor in vitro (SC cultures), applying biochemical and functional approaches (Dememes et al., 1995; Dezawa et al., 1998; Mayer et al., 1998; Verkhratsky and Steinhauser, 2000; Altevogt et al., 2002; Baker, 2002; Fields and Burnstock, 2006; Loreti et al., 2006; Magnaghi et al., 2006; Saitoh and Araki, 2010; Procacci et al., 2012; Nualart-Marti et al., 2013). A summary with the so far-identified SC r.
