Abstract
Vagus nerve innervates several organs including the heart, stomach, and pancreas among others. Somas of sensory neurons that project through the vagal nerve are located in the nodose ganglion. The presence of purinergic receptors has been reported in neurons and satellite glial cells in several sensory ganglia. In the nodose ganglion, calcium depletion-induced increases in neuron activity can be partly reversed by P2X7 blockers applied directly into the ganglion. The later suggest a possible role of P2X7 receptors in the modulation of neuronal activity within this sensory ganglion. We aimed to characterize the response to P2X7 activation in nodose ganglion neurons under physiological conditions. Using an ex vivo preparation for electrophysiological recordings of the neural discharges of nodose ganglion neurons, we found that treatments with ATP induce transient neuronal activity increases. Also, we found a concentration-dependent increase in neural activity in response to Bz-ATP (ED50 = 0.62 mM, a selective P2X7 receptor agonist), with a clear desensitization pattern when applied every ~ 30 s. Electrophysiological recordings from isolated nodose ganglion neurons reveal no differences in the responses to Bz-ATP and ATP. Finally, we showed that the P2X7 receptor was expressed in the rat nodose ganglion, both in neurons and satellite glial cells. Additionally, a P2X7 receptor negative allosteric modulator decreased the duration of Bz-ATP-induced maximal responses without affecting their amplitude. Our results show the presence of functional P2X7 receptors under physiological conditions within the nodose ganglion of the rat, and suggest that ATP modulation of nodose ganglion activity may be in part mediated by the activation of P2X7 receptors.
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Abbreviations
- ATP:
-
Adenosine triphosphate
- Bz-ATP:
-
2′(3′)-O-(4-Benzoylbenzoyl)adenosine 5′-triphosphate triethylammonium salt
- ΔƒmaxATP:
-
Maximal response induced by ATP
- ƒVN :
-
Vagus nerve frequency of discharge
- ΔƒVN :
-
Changes in vagus nerve frequency of discharge
- D:
-
Applied dose
- DRG:
-
Dorsal root ganglion
- GABA:
-
γ-Aminobutyric acid
- ED50 :
-
Dose that evoked half-maximal response
- HBSS:
-
Hanks' balanced salt solution
- NG:
-
Nodose ganglion
- NPJc:
-
Nodose-petrosal-jugular complex
- P2X:
-
ATP-gated receptor cation channel family
- P2Y:
-
ATP-activated GPCR family
- Panx1:
-
Pannexin 1
- PBS:
-
Phosphate buffered saline
- S:
-
Hill slope factor
- SE:
-
Standard error
- VN:
-
Vagus nerve
- Ymax :
-
Mean maximal response
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Funding
This work was supported by Grants from the National Fund for Scientific and Technological Development (FONDECYT) #1160227 (MAR), #1220950 (RDR), and #1130177 (JA) and the Basal Centre of Excellence in Aging and Regeneration (AFB 170005 and ACE 210009). Millennium Nucleus for the Study of Pain (MiNuSPain). MiNuSPain is supported by the Millennium Scientific Initiative NCN19_038 of the Ministry of Science, Technology, Knowledge and Innovation, Chile and FONDEQUIP EQM140100.
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JA, JV, RDR, ED-J, MR-J, AAC, CC, and MAR, designed and/or performed the experiments; JA, and MAR, analyzed data and JA, RDR, CC, and MAR wrote and edited the paper. JA, RDR, and MAR reviewed the final version.
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Alcayaga, J., Vera, J., Reyna-Jeldes, M. et al. Activation of Intra-nodose Ganglion P2X7 Receptors Elicit Increases in Neuronal Activity. Cell Mol Neurobiol 43, 2801–2813 (2023). https://doi.org/10.1007/s10571-023-01318-8
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DOI: https://doi.org/10.1007/s10571-023-01318-8