Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones
Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones
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DOI：
10.1007/s00424-008-0542-1
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发表时间：
2008-11-01
影响因子：
4.5
通讯作者：
Yoshida, Munehito
中科院分区：
文献类型：
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作者：
Miyazaki, Nobuyuki;Nakatsuka, Terumasa;Yoshida, Munehito
虽然腺苷是一种重要的神经调质，但其在脊髓水平调节运动功能的作用知之甚少。在本研究中，我们研究了腺苷对兴奋性突触传递和神经元死亡的实验性缺血诱导的全细胞膜片钳记录从第IX层神经元在脊髓切片。腺苷能显著降低几乎所有神经元的兴奋性突触后电流（mEPSC），这种电流能被A（1）受体激动剂N-6-环戊基腺苷（CPA）模拟，并被A（1）受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX）抑制。有趣的是，在DPCPX存在下，腺苷增加了神经元亚群中的mEPSC频率。在这些神经元中，A（2A）受体激动剂2-[4-（2-carbonylethyl）-phenethylamino] 5 '-N-thylcarboxamidoadenosine（CGS 21680）增加mEPSC频率。腺苷还诱导了外向电流，被阻断的Cs+和四乙基铵加入到贴片吸管溶液中，并抑制在Ba 2+的存在下。腺苷诱导的外向电流被CPA所模拟，但不被CGS 21680所模拟，并被DPCPX所抑制。此外，灌流缺血模拟介质（ISM）产生的濒死内向电流在所有的神经元测试。腺苷和CPA均能显著延长ISM诱发的内向电流，而CGS 21680则无此作用。这些结果表明，腺苷受体的功能表达在前和突触后位点的第九层神经元和它们的激活可能会产生多种影响运动功能。此外，本研究还为腺苷的神经保护作用中A（1）受体的参与提供了细胞基础。
Although adenosine is an important neuromodulator, its role in modulating motor functions at the level of the spinal cord is poorly understood. In the present study, we investigated the effects of adenosine on excitatory synaptic transmission and neuronal death induced by experimental ischaemia by using whole-cell patch-clamp recordings from lamina IX neurones in spinal cord slices. Adenosine significantly decreased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in almost all neurones examined that could be mimicked by an A(1) receptor agonist, N-6-cyclopentyladenosine (CPA), and inhibited by an A(1) receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). Interestingly, adenosine increased mEPSC frequency in the presence of DPCPX in a subpopulation of neurones. In these neurones, an A(2A) receptor agonist, 2-[4-(2-carbonylethyl)-phenethylamino]5'-N-thylcarboxamidoadenosine (CGS21680), increased mEPSC frequency. Adenosine also induced an outward current that was blocked by the addition of Cs+ and tetraethylammonium into the patch-pipette solution and inhibited in the presence of Ba2+. The adenosine-induced outward current was mimicked by CPA, but not CGS21680, and inhibited by DPCPX. Moreover, superfusing with ischaemia simulating medium (ISM) generated an agonal inward current in all of the neurones tested. The latencies of the inward currents induced by ISM were significantly prolonged by adenosine or CPA, but not by CGS21680. These results suggest that adenosine receptors are functionally expressed in both the pre- and postsynaptic sites of lamina IX neurones and that their activation may exert multiple effects on motor function. Moreover, this study has provided a cellular basis for an involvement of A(1) receptors in the neuroprotective actions of adenosine.