ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in dorsal horn neurons of the rat spinal cord
ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in dorsal horn neurons of the rat spinal cord
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DOI：
10.1523/jneurosci.21-17-06522.2001
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发表时间：
2001-09-01
影响因子：
5.3
通讯作者：
Gu, JG
中科院分区：
文献类型：
--
作者：
Nakatsuka, T;Gu, JG
突触前ATP2X受体被认为在调节脊髓第一感觉突触释放谷氨酸方面发挥作用。用脊髓切片和膜片钳记录大鼠脊髓V层背角神经元，发现α，β-亚甲基-三磷酸腺苷(α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷(α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷(α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-β-亚甲基-三磷酸腺苷，α-Ca(2+)通道阻断剂La(3+)不能阻断α-Betam-ATP对mEPSC频率的增加，但在不含Ca(2+)的浴液中可被阻断。P2受体拮抗剂pyridoxalphosphate-6-azophenyl-2‘，4’-disulfonic酸(PPADS)在10微米时可完全阻断α-β-三磷酸腺苷对mEPSC频率的增加。此外，刺激背根诱发的EPSCs可被α-β-ATP和外源性ATPase抑制剂ARL67156增强，而在P2受体拮抗剂PPADS(10um)和苏拉明(5um)的存在下则被抑制。这些化合物对诱发的EPSCs的影响与初级传入中枢终末谷氨酸释放概率的变化有关。我们的结果表明，α-β-ATP敏感的P2X受体在脊髓兴奋性感觉突触传递中起着重要的调节作用，并提示了内源性ATP的潜在作用。
Presynaptic ATP P2X receptors have been proposed to play a role in modulating glutamate release from the first sensory synapse in the spinal cord. Using spinal cord slice preparations and patch-clamp recordings from dorsal horn neurons in lamina V of the rat spinal cord, we showed that the activation of P2X receptors by alpha,beta -methylene- ATP (alpha betam-ATP) resulted in a large increase in the frequency of spontaneous EPSCs (sEPSCs) and miniature EPSCs (mEPSCs). The increases in mEPSC frequency by alpha betam-ATP were not blocked by the Ca(2+) channel blocker, 30 muM La(3+), but were abolished in a bath solution when Ca(2+) was omitted. The increases in mEPSC frequency by alpha betam-ATP were blocked completely by the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) at 10 muM. Furthermore, the EPSCs evoked by dorsal root stimulation were potentiated by alpha betam-ATP as well as by the ecto-ATPase inhibitor ARL67156 and were depressed in the presence of P2 receptor antagonists PPADS (10 muM) and suramin (5 muM). The effects of these compounds on the evoked EPSCs were associated with the changes in glutamate release probability of primary afferent central terminals. Our results indicate that alpha betam-ATP-sensitive P2X receptors play a significant role in modulating excitatory sensory synaptic transmission in the spinal cord, and the potential role of endogenous ATP is suggested.