Mechanism of the transmitter release facilitation through activation of presynaptic ATP receptors in the brainstem

P2X受体（P2X- rs）是atp门控通道，可渗透于倾向于Ca^<2+>的阳离子。我们在体外孤束核（外源ATP对自主神经流出有深远影响的大脑部分）中，记录了来自二级神经元的电压依赖性Na^+通道被阻断的微型兴奋性突触后电流（mEPSCs）。ATP或α，β-亚甲基ATP （α,βmATP）激活突触前P2X-Rs不仅可以增强谷氨酸的释放，而且即使在电压依赖性钙通道（VDCCs）完全阻断的情况下也可以重新启动谷氨酸的释放。αβmATP对谷氨酸释放的促进作用被px - r拮抗剂吡啶多磷酸-6-偶氮苯基-2′，4′-二磺酸（PPADS）和高浓度（但不是低浓度）亚型选择性拮抗剂2 bbbb3,3′- o -（2,4,6-三硝基苯）- atp （TNP-ATP）完全消除。尽管αβmATP明显增加了兴奋性突触后事件的频率，但孤立束刺激评估的突触失败率并未受到显著影响。在阻断vdc依赖性突触传递的情况下，P2X-R激动剂引起的微兴奋性突触后电位足以触发突触后细胞的动作电位。这些结果表明，即使在没有突触前兴奋的情况下，细胞外ATP浓度的升高也会促进兴奋性传递，从而导致自主神经网络的激活。

P2X receptors (P2X-Rs) are ATP-gated channels permeable to cations inclining Ca^<2+>. We recorded miniature excitatory postsynaptic currents (mEPSCs) under blockade of voltage-dependent Na^+ channels from second-order neurons in the nucleus tractus solitarii in vitro, a part of the brain where exogenous ATP has profound effects on autonomic outflow. Activation of presynaptic P2X-Rs with ATP or α,β-methylene ATP (α,βmATP) not only enhanced the release of glutamate, but could initiate it de novo even when voltage-dependent calcium channels (VDCCs) were completely blocked. This facilitating effect of αβmATP on the glutamate release was abolished completely by a P2X-R antagonist pyridoxalphosphate-6-azophenyl-2',4' -disulphonic acid (PPADS) and by a high, but not a low, concentration of a subtype-selective antagonist 2 > ,3 ' -O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP). Despite manifest increase in the frequency of excitatory postsynaptic events by αβmATP, the rate of the synaptic failures as evaluated by solitary tract stimulation was not significantly affected. The miniature excitatory postsynaptic potentials elicited with P2X-R agonists recorded under blockade of VDCC-dependent synaptic transmission were sufficient to trigger action potentials in the postsynaptic cell. These results show that a rise in extracellular ATP concentration promotes excitatory transmission even in the absence of presynaptic excitation, leading to a consequent activation of the autonomic networks.