Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors
Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors
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DOI：
10.1113/jphysiol.2003.047894
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发表时间：
2003-09-01
影响因子：
5.5
通讯作者：
Schlichter, R
中科院分区：
文献类型：
--
作者：
Hugel, S;Schlichter, R
在体外培养的新生大鼠脊髓背角浅层神经元上，采用膜片钳技术研究了GABA在突触前对单一突触连接释放的调节作用。由于ATP可在DH神经元间约2/3的GABA能突触中与GABA共释放，并可在细胞外空间迅速代谢为腺苷，因此我们研究了可能作为抑制性自身受体的A1腺苷受体和GABA（B）受体的潜在作用。腺苷和GABA（B）受体激动剂降低电诱发GABA能抑制性突触后电流（eIPSC）的幅度以及GABA能微型IPSC的频率，表明这些物质的突触前作用。腺苷的作用可被A1受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX）阻断。腺苷和GABA（B）激动剂的作用是闭塞性的，表明A1和GABA（B）受体参与的信号传导通路的功能性会聚。A1和GABA（B）拮抗剂以超累加方式增加eIPSC的幅度，表明这些受体被周围的腺苷和GABA紧张激活。此外，尽管所有GABA能DH神经元上都存在功能性突触前A1和GABA（B）受体，但使用一系列电刺激，我们仅在神经元共释放ATP和GABA的情况下，才能够阐明突触前A1和GABAB自身受体的阶段性（活性依赖性）激活。A1和GABA（B）自身受体对GABA释放的这种选择性、会聚性和活性依赖性抑制可能在生理条件下和/或病理性疼痛状态的发展过程中调节突触后DH神经元的整合特性。
Perforated patch clamp recordings were performed on cultured superficial neonatal rat dorsal horn (DH) spinal cord neurones in order to study the presynaptic modulation of GABA release at unitary synaptic connections. Since ATP can be coreleased with GABA at about two-thirds of GABAergic synapses between DH neurones, and can be rapidly metabolized to adenosine in the extracellular space, we investigated the potential role of A1 adenosine receptors and GABA(B) receptors which might function as inhibitory autoreceptors. Adenosine and GABA(B) receptor agonists reduced the amplitude of electrically evoked GABAergic inhibitory postsynaptic currents (eIPSCs) as well as the frequency of GABAergic miniature IPSCs, suggesting a presynaptic action of these substances. The actions of adenosine were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The effects of adenosine and GABA(B) agonists were occlusive, indicating a functional convergence of the signalling pathways engaged by A1 and GABA(B) receptors. A1 and GABA(B) antagonists increased the amplitude of eIPSCs in a supra-additive manner, suggesting a tonic activation of these receptors by ambient adenosine and GABA. Moreover, using trains of electrical stimulations, we were able to unravel a phasic (activity-dependent) activation of presynaptic A I and GABAB autoreceptors only in the case of neurones coreleasing ATP and GABA, despite the presence of functional presynaptic A1 and GABA(B) receptors on all GABAergic DH neurones. This selective, convergent and activity-dependent inhibition of GABA release by A1 and GABA(B) autoreceptors might modulate the integrative properties of postsynaptic DH neurones under physiological conditions and/or during the development of pathological pain states.