Role of P2Y1 receptor in astroglia-to-neuron signaling at dorsal spinal cord.
Several studies have shown that astrocytes release neurotransmitters into the extracellular space that may then activate receptors on nearby neurons. In the present study, the actions of adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS)-activated astrocyte conditioned medium (ADPbetaS-ACM) on cultured dorsal spinal cord neurons were evaluated by using confocal laser scanning microscopy and whole-cell patch-clamp recording. ADPbetaS caused astrocytic glutamate efflux (43 microM), which in turn induced inward currents in dorsal horn neurons with short time in culture. The inward currents were abolished by 2-amino-5-phosphonlanoicacid (AP-5; NMDAR antagonist) plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDAR antagonist) but were unaffected by MRS2179 (selective P2Y(1) receptor antagonist). Furthermore, N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) was used to block glutamate release from astrocytes. As a result, ADPbetaS-ACM-induced inward currents in neurons were significantly blocked. On the other hand, both NMDAR and non-NMDAR were involved in ADPbetaS-ACM (concentration was diluted to one-tenth)-evoked small [Ca(2+)](i) transients in neurons. Under this condition, the values of glutamate concentrations in the medium are close to values for extracellular glutamate concentrations under physiological conditions. For this reason, it is possible that astrocyte-derived glutamate is important for distant neuron under physiological conditions at dorsal spinal cord. These observations indicate that astrocytic P2Y(1) receptor activation triggered glutamate efflux, which acts on distant neurons to elevate calcium levels or acts on nearby neurons to evoke inward current. Finally, our results support the conclusion that the astrocytic P2Y(1) receptor plays an important role in bidirectional communication between astrocytes and neurons.
Zeng
Jun-Wei
JW
Department of Neurobiology, College of Medicine, Third Military Medical University, Chongqing, China.
Liu
Xiao-Hong
XH
Zhao
Yan-Dong
YD
Xiao
Zhi
Z
He
Wen-Juan
WJ
Hu
Zhi-An
ZA
Ruan
Huai-Zhen
HZ
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D017470:Receptors, Glutamate; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D018698:Glutamic Acid; D000244:Adenosine Diphosphate