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bioRxiv · 10.1101/702563

A role for the P2Y1 receptor in nonsynaptic cross-depolarization in the rat dorsal root ganglia

Carvalho, G.·Mulpuri, Y.·Damasio, A.·Spigelman, I.
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Abstract

Non-synaptic transmission is pervasive throughout the nervous system. It appears especially prevalent in peripheral ganglia, where non-synaptic interactions between neighboring cell bodies have been described in both physiological and pathological conditions, a phenomenon referred to as cross-depolarization (CD) and thought to play a role in sensory processing and chronic pain. CD has been proposed to be mediated by a chemical agent, but its identity has remained elusive. Here, we report that in the rat dorsal root ganglion (DRG), the P2Y1 purinergic receptor (P2RY1) plays an important role in regulating CD. The effect of P2RY1 is cell-type specific: pharmacological blockade of P2RY1 inhibited CD in A-type neurons while enhancing it in unmyelinated C-type cells. In the nodose ganglion of the vagus, CD requires extracellular calcium in a large percentage of cells. In contrast, we show that in the DRG extracellular calcium appears to play no major role, pointing to a mechanistic difference between the two peripheral ganglia. Furthermore, we show that DRG glial cells also play a cell-type specific role in CD regulation. Fluorocitrate-induced glial inactivation had no effect on A-cells but enhanced CD in C-cells. These findings shed light on the mechanism of CD in the DRG and pave the way for further analysis of non-synaptic neuronal communication in sensory ganglia.\n\nHighlightsO_LIThe purinergic receptor P2RY1 plays a regulatory role in non-synaptic crossdepolarization (CD) in the mammalian DRG\nC_LIO_LIThe effect of P2RY1 is cell type-specific: it enhances CD in myelinated A-type neurons, but inhibits it in unmyelinated C-cells\nC_LIO_LICD in the DRG does not require extracellular calcium. This is in contrast with the nodose ganglion, where extracellular calcium plays an important role in nonsynaptic interactions\nC_LIO_LICD is also modulated by DRG glial cells. Glia selectively inhibit CD in C-type neurons\nC_LI

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Carvalho, G., Mulpuri, Y., Damasio, A., Spigelman, I.. 2019-07-14. A role for the P2Y1 receptor in nonsynaptic cross-depolarization in the rat dorsal root ganglia. https://doi.org/10.1101/702563

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