Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

Abstract

Astrocytes communicate with neurons, endothelial and other glial cells through transmission of intercellular calcium signals. Satellite glial cells (SGCs) in sensory ganglia share several properties with astrocytes, but whether this type of communication occurs between SGCs and sensory neurons has not been explored. In the present work we used cultured neurons and SGCs from mouse trigeminal ganglia to address this question. Focal electrical or mechanical stimulation of single neurons in trigeminal ganglion cultures increased intracellular calcium concentration in these cells and triggered calcium elevations in adjacent glial cells. Similar to neurons, SGCs responded to mechanical stimulation with increase in cytosolic calcium that spread to the adjacent neuron and neighboring glial cells. Calcium signaling from SGCs to neurons and among SGCs was diminished in the presence of the broad-spectrum P2 receptor antagonist suramin (50 µM) or in the presence of the gap junction blocker carbenoxolone (100 µM), whereas signaling from neurons to SGCs was reduced by suramin, but not by carbenoxolone. Following induction of submandibular inflammation by Complete Freund's Adjuvant injection, the amplitude of signaling among SGCs and from SGCs to neuron was increased, whereas the amplitude from neuron to SGCs was reduced. These results indicate for the first time the presence of bidirectional calcium signaling between neurons and SGCs in sensory ganglia cultures, which is mediated by the activation of purinergic P2 receptors, and to some extent by gap junctions. Furthermore, the results indicate that not only sensory neurons, but also SGCs release ATP. This form of intercellular calcium signaling likely plays key roles in the modulation of neuronal activity within sensory ganglia in normal and pathological states.

Satellite glial cells: more than just ‘rings around the neuron’

“…Because SGCs have P2 receptors and are also coupled by gap junctions, they have the potential to sustain calcium waves. This is now demonstrated by Suadicani et al (2010) and serves as another evidence for the similarity between SGCs and astrocytes. This article also provides evidence that SGCs can release ATP, which is one of the main 'gliotransmitters'.…”

Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process

“…The broad-spectrum purinergic receptor blocker suramin (P7643, 50 μM; Sigma-Aldrich) or nucleotide-degrading enzyme apyrase (A7646, 6.8 U/mL; Sigma-Aldrich), was used to explore the role of P2Rs in intercellular signaling (62,63). Membrane currents were measured in response to stimulation of distal regions of an unapposed cell process in the presence and absence of suramin (incubation for 2-3 min).…”

P2Y purinergic receptors: New targets for analgesic and antimigraine drugs

“…In fact, the amplitude of Ca-signaling among SGCs and between SGC-to-neuron was increased following induction of submandibular inflammation by CFA injection, whereas the amplitude of Casignaling from neuron-to-SGC was reduced [60]. Moreover, the intracellular calcium response to ATP was mediated by P2Y receptors in control tissues, whereas the response was predominantly due to ionotropic P2X receptors after CFA-induced inflammation, suggesting that inflammatory conditions not only induce a large increase in the sensitivity of SGCs to ATP, but also a switch in ATP signaling through P2Y receptors to P2X receptors [85].…”

“…As detailed below, their contribution to nociception is now firmly acknowledged, both in the periphery and in the CNS (with a primary role played here by microglia and astrocytes) [58] . Within sensory ganglia, the somata of sensory neurons are surrounded and wrapped by a network of satellite glial cells (SGCs), which continually monitor the extracellular milieu and exchange information with one another and with neurons as well, so profoundly affecting neuronal firing and, ultimately, the transmission of painful sensations [59,60]. Thus, targeting glial cells with specific pharmacological compounds has recently emerged as an exciting opportunity for the development of new and effective painkillers.…”

“…Those P2 purinergic receptors expressed by SGCs participate primarily in bidirectional neuron-glial communication [60], thanks to the somatic release of ATP within the sensory ganglion [62]. Released ATP may activate P2X7 receptors in SGCs, leading to the release of TNFα, which in turn can potentiate P2X3-mediated ATP currents in neurons (see also below) [62].…”