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Role of P2Y 1 receptor in astroglia‐to‐neuron signaling at dorsal spinal cord
Author(s) -
Zeng JunWei,
Liu XiaoHong,
Zhao YanDong,
Xiao Zhi,
He WenJuan,
Hu ZhiAn,
Ruan HuaiZhen
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22108
Subject(s) - glutamate receptor , nmda receptor , ppads , astrocyte , cnqx , neuron , extracellular , neuroscience , spinal cord , biology , adenosine , antagonist , receptor , chemistry , biophysics , microbiology and biotechnology , endocrinology , ampa receptor , purinergic receptor , central nervous system , biochemistry
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 μM), 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. © 2009 Wiley‐Liss, Inc.