Purinergic P2X receptors presynaptically increase glutamatergic synaptic transmission in dorsolateral periaqueductal gray.
Purinergic P2X receptors have been reported to be 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 alpha, beta-methylene ATP (a P2X receptor agonist), in the concentration of 50 microM, 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, alpha, beta-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, immunofluorescent 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.
Xing
Jihong
J
Heart and Vascular Institute and Department of Medicine, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Lu
Jian
J
Li
Jianhua
J
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010487:Periaqueductal Gray / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016708:Synaptophysin / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D016708:Synaptophysin; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate