Purinergic P2X receptors presynaptically increase glutamatergic synaptic transmission in dorsolateral periaqueductal gray

Abstract

Purinergic P2X receptors have been reported to present in regions of the midbrain periaqueductal gray (PAG). The purpose of this study was to determine the role of presynaptic P2X receptors in modulating excitatory and inhibitory synaptic inputs to the dorsolateral PAG (dl-PAG), which has abundant neuronal connections. First, whole cell voltage-clamp recording was performed to obtain excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) of the dl-PAG neurons. Our data show that α, β-methylene ATP (a P2X receptors agonist), in the concentration of 50 µM, significantly increased the frequency of miniature EPSCs without altering the amplitude of miniature EPSCs in eight tested neurons. The effects were attenuated by PPADS, an antagonist to P2X receptors. Furthermore, α, β-methylene ATP increased the amplitude of evoked EPSCs, and decreased the paired-pulse ratio of eEPSCs in ten neurons. In contrast, activation of P2X had no distinct effect on IPSCs. In addition, immunofluoresent methods demonstrate that P2X labeling was co-localized with a presynaptic marker, synaptophysin, in the dl-PAG. The results of the current study provide the first evidence indicating that P2X receptors facilitate glutamatergic synaptic transmission in the dl-PAG via presynaptic mechanisms. SectionNeurophysiology, Neuropharmacology and other forms of Intercellular Communication

P2X receptor overexpression induced by soluble oligomers of amyloid beta peptide potentiates synaptic failure and neuronal dyshomeostasis in cellular models of Alzheimer's disease

“…1Ad,1B). This unexpected result can be interpreted as a compensatory response to the effect of P2XR activation on the neuronal network (without SO-Aβ), and correlate with previous effects reported in the literature (Xing et al, 2008).…”

No more pain upon Gq‐protein‐coupled receptor activation: role of endocannabinoids

“…It remains to be further elucidated if these G q PCRs can activate the G q PCR–PLC–DAGL–2‐AG retrograde disinhibition mechanism and lead to analgesia. In addition, several neurotransmitters in the PAG, the receptors of which couple to cation channels, have been reported to be antinociceptive, such as neuropeptide FF (Wei et al ., ; Panula et al ., ), ATP (P2X receptor; Xing et al ., ; Xiao et al ., ), somatostatin (SST2 receptor; Tallent et al ., ; Schindler et al ., ), neuropeptide Y (Wang et al ., , ) and endothelin‐1 (D'Amico et al ., ). It will be of interest to examine if activation of these ionotropic receptors by these neurotransmitters will activate glutamatergic neurons and increase glutamate release, like substance P, neurotensin and CCK, to initiate the mGluR5–PLC–DAGL–2‐AG retrograde disinhibition mechanism in the PAG and lead to analgesia.…”

Facilitation of Neurotransmitter and Hormone Release by P2X Purinergic Receptors

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