TY - JOUR
T1 - BzATP Activates Satellite Glial Cells and Increases the Excitability of Dorsal Root Ganglia Neurons In Vivo
AU - Chen, Zhiyong
AU - Zhang, Chi
AU - Song, Xiaodan
AU - Cui, Xiang
AU - Liu, Jing
AU - Ford, Neil C.
AU - He, Shaoqiu
AU - Zhu, Guangwu
AU - Dong, Xinzhong
AU - Hanani, Menachem
AU - Guan, Yun
N1 - Funding Information:
This study was conducted at Johns Hopkins University and was supported by grants NS070814 (Y.G.), NS110598 (Y.G.) and NS117761 (Y.G.) from the National Institutes of Health (Bethesda, MD, USA). This study was subsidized by the Lerner Family Fund for Pain Research and a grant from the Neurosurgery Pain Research Institute at Johns Hopkins University (Y.G). This work was facilitated by the Pain Research Core funded by the Blaustein Fund and the Neurosurgery Pain Research Institute at Johns Hopkins University. M.H. was supported by the Israel Science Foundation (1297/18) and the United States–Israel Binational Science Foundation (BSF, 2019076). The funders had no role in study design, data collection, data interpretation, or in the decision to submit the work for publication.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - The purinergic system plays an important role in pain transmission. Recent studies have suggested that activation of P2-purinergic receptors (P2Rs) may be involved in neuron-satellite glial cell (SGC) interactions in the dorsal root ganglia (DRG), but the details remain unclear. In DRG, P2X7R is selectively expressed in SGCs, which closely surround neurons, and is highly sensitive to 3’-O-(4-Benzoyl) benzoyl-ATP (BzATP). Using calcium imaging in intact mice to survey a large number of DRG neurons and SGCs, we examined how intra-ganglionic purinergic signaling initiated by BzATP affects neuronal activities in vivo. We developed GFAP-GCaMP6s and Pirt-GCaMP6s mice to express the genetically encoded calcium indicator GGCaM6s in SGCs and DRG neurons, respectively. The application of BzATP to the ganglion induced concentration-dependent activation of SGCs in GFAP-GCaMP6s mice. In Pirt-GCaMP6s mice, BzATP initially activated more large-size neurons than small-size ones. Both glial and neuronal responses to BzATP were blocked by A438079, a P2X7R-selective antagonist. Moreover, blockers to pannexin1 channels (probenecid) and P2X3R (A317491) also reduced the actions of BzATP, suggesting that P2X7R stimulation may induce the opening of pannexin1 channels, leading to paracrine ATP release, which could further excite neurons by acting on P2X3Rs. Importantly, BzATP increased the responses of small-size DRG neurons and wide-dynamic range spinal neurons to subsequent peripheral stimuli. Our findings suggest that intra-ganglionic purinergic signaling initiated by P2X7R activation could trigger SGC-neuron interaction in vivo and increase DRG neuron excitability.
AB - The purinergic system plays an important role in pain transmission. Recent studies have suggested that activation of P2-purinergic receptors (P2Rs) may be involved in neuron-satellite glial cell (SGC) interactions in the dorsal root ganglia (DRG), but the details remain unclear. In DRG, P2X7R is selectively expressed in SGCs, which closely surround neurons, and is highly sensitive to 3’-O-(4-Benzoyl) benzoyl-ATP (BzATP). Using calcium imaging in intact mice to survey a large number of DRG neurons and SGCs, we examined how intra-ganglionic purinergic signaling initiated by BzATP affects neuronal activities in vivo. We developed GFAP-GCaMP6s and Pirt-GCaMP6s mice to express the genetically encoded calcium indicator GGCaM6s in SGCs and DRG neurons, respectively. The application of BzATP to the ganglion induced concentration-dependent activation of SGCs in GFAP-GCaMP6s mice. In Pirt-GCaMP6s mice, BzATP initially activated more large-size neurons than small-size ones. Both glial and neuronal responses to BzATP were blocked by A438079, a P2X7R-selective antagonist. Moreover, blockers to pannexin1 channels (probenecid) and P2X3R (A317491) also reduced the actions of BzATP, suggesting that P2X7R stimulation may induce the opening of pannexin1 channels, leading to paracrine ATP release, which could further excite neurons by acting on P2X3Rs. Importantly, BzATP increased the responses of small-size DRG neurons and wide-dynamic range spinal neurons to subsequent peripheral stimuli. Our findings suggest that intra-ganglionic purinergic signaling initiated by P2X7R activation could trigger SGC-neuron interaction in vivo and increase DRG neuron excitability.
KW - calcium imaging
KW - dorsal root ganglion
KW - mice
KW - pain
KW - purinergic receptor
KW - satellite glial cell
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U2 - 10.3390/cells11152280
DO - 10.3390/cells11152280
M3 - Article
C2 - 35892578
AN - SCOPUS:85135130717
SN - 2073-4409
VL - 11
JO - Cells
JF - Cells
IS - 15
M1 - 2280
ER -