Opening of pannexin- and connexin-based channels increases the excitability of nodose ganglion sensory neurons

Abstract

Satellite glial cells (SGCs) are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents the formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with sensory neurons. However, the molecular mechanism involved in this cellular communication is unknown. In the central nervous system (CNS), astrocytes present connexin43 (Cx43) hemichannels and pannexin1 (Panx1) channels, and the opening of these channels allows the release of signal molecules, such as ATP and glutamate. We propose that these channels could play a role in glia-neuron communication in sensory ganglia. Therefore, we studied the expression and function of Cx43 and Panx1 in rat and mouse nodose-petrosal-jugular complexes (NPJcs) using confocal immunofluorescence, molecular and electrophysiological techniques. Cx43 and Panx1 were detected in SGCs and in sensory neurons, respectively. In the rat and mouse, the electrical activity of vagal nerve increased significantly after nodose neurons were exposed to a Ca2+/Mg2+-free solution, a condition that increases the open probability of Cx hemichannels. This response was partially mimicked by a cell-permeable peptide corresponding to the last 10 amino acids of Cx43 (TAT-Cx43CT). Enhanced neuronal activity was reduced by Cx hemichannel, Panx1 channel and P2X7 receptor blockers. Moreover, the role of Panx1 was confirmed in NPJc, because in those from Panx1 knockout mice showed a reduced increase of neuronal activity induced by Ca2+/Mg2+-free extracellular conditions. The data suggest that Cx hemichannels and Panx channels serve as paracrine communication pathways between SGCs and neurons by modulating the excitability of sensory neurons.

Molecular Signaling and Dysfunction of the Human Reactive Enteric Glial Cell Phenotype

“…This is a novel protective mechanism that may provide glial and neuronal protection in an effort to preserve the normal neural-glial environment in human ENS. Free radicals increase the permeability of Cx43 hemichannels to large molecules or their open probability 60 and they are involved in Ca 2+ waves in hEGC 10 .…”

Systemic inflammation activates satellite glial cells in the mouse nodose ganglion and alters their functions

“…Knowledge on the functional properties of SGCs in the NG is scarce, and information on the communication among these cells has not been available. Recently Retamal et al () have shown that SGCs rat NG are endowed with Cx43 hemichannels and Panx1 channels, which are unapposed channels ortholog to invertebrate innexin gap junctions (Bennett et al, ). These channels are large enough to allow the release of ATP and other substances, thus enabling SGCs to modulate neuronal activity.…”

Gap junction gene and protein families: Connexins, innexins, and pannexins

“…The only human gene mutation reported to date encodes a non-functional PANX1 variant that does not inhibit the function of wild type PANX1; it was found in a patient (homozygous for this allele) with disorders in several organs [49]. Investigations of pannexin-null mice have also implicated pannexins in contributing to protection from ischemic stroke injury [4,21], modulation of neuronal excitability and learning [43,44], bone development [27], narcotic withdrawal [14], and sleep-wake cycle regulation and behavior [29]. …”