Excitatory actions of GABA mediate severe-hypoxia-induced depression of neuronal activity in the pond snail (Lymnaea stagnalis)
Excitatory actions of GABA mediate severe-hypoxia-induced depression of neuronal activity in the pond snail (Lymnaea stagnalis)
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DOI：
10.1242/jeb.02553
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发表时间：
2006-11-15
影响因子：
2.8
通讯作者：
Woodin, Melanie A.
中科院分区：
文献类型：
--
作者：
Cheung, Una;Moghaddasi, Mehrnoush;Woodin, Melanie A.
为了表征严重缺氧对神经元活动的影响，从神经元中分离的中央环神经节的滞流神经元进行了长期的细胞内记录。当一个神经元在常氧条件下处于静息状态时，受到严重缺氧的影响，动作电位放电频率降低38%（从2.4-1.5峰/s），静息膜电位从-70.3 mV超极化至-75.1 mV。用拮抗剂甲碘荷包牡丹碱（100 mmol 1（-1））阻断GABA（A）受体介导的突触传递可使神经元活性降低36%，并阻止对严重缺氧反应的任何进一步变化，表明GABA能神经传递介导了严重缺氧诱导的神经元活性降低。将100 μ mol l（-1）GABA喷到细胞体上产生兴奋性反应，其特征为动作电位（AP）放电的瞬时增加，在严重缺氧时显著降低。用Na+/K+/Cl-（NKCC 1）协同转运蛋白拮抗剂布美他尼（100 μ mol-1）干扰细胞内氯离子浓度，AP放电减少40%，这与GABA是成年人CNS中的兴奋性神经递质一致。总之，这些研究表明，严重缺氧降低NKCC 1的活性，导致兴奋性GABA能传递减少，这导致静息膜电位（V-m）超极化，从而降低AP频率。
To characterize the effect of severe hypoxia on neuronal activity, long-term intracellular recordings were made from neurones in the isolated central ring ganglia of Lymnaea stagnalis. When a neurone at rest in normoxia was subjected to severe hypoxia, action potential firing frequency decreased by 38% ( from 2.4-1.5 spikes s(-1)), and the resting membrane potential hyperpolarized from -70.3 to -75.1 mV. Blocking GABA(A) receptor-mediated synaptic transmission with the antagonist bicuculline methiodide (100 mmol 1(-1)) decreased neuronal activity by 36%, and prevented any further changes in response to severe hypoxia, indicating that GABAergic neurotransmission mediates the severe hypoxia-induced decrease in neuronal activity. Puffing 100 mu mol l(-1) GABA onto the cell body produced an excitatory response characterized by a transient increase in action potential (AP) firing, which was significantly decreased in severe hypoxia. Perturbing intracellular chloride concentrations with the Na+/K+/Cl-( NKCC1) cotransporter antagonist bumetanide (100 mu mol 1(-1)) decreased AP firing by 40%, consistent with GABA being an excitatory neurotransmitter in the adult Lymnaea CNS. Taken together, these studies indicate that severe hypoxia reduces the activity of NKCC1, leading to a reduction in excitatory GABAergic transmission, which results in a hyperpolarization of the resting membrane potential (V-m) and as a result decreased AP frequency.