Multiple types of GABAA receptors mediate inhibition in brain stem parasympathetic cardiac neurons in the nucleus ambiguus
Multiple types of GABAA receptors mediate inhibition in brain stem parasympathetic cardiac neurons in the nucleus ambiguus
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DOI：
10.1152/jn.00590.2006
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发表时间：
2006-12-01
影响因子：
2.5
通讯作者：
Mendelowitz, David
中科院分区：
文献类型：
--
作者：
Bouairi, Euguenia;Kamendi, Harriet;Mendelowitz, David
最近的工作表明，神经元可以具有不同类型的γ-氨基丁酸A型（GABA（A））受体，介导相位抑制性突触后电流（IPSC）和紧张性电流。本研究探讨了GABA能突触电流的多样性，在副交感神经心脏抑制神经元，接受节律性爆发的GABA能神经传递。局部应用gabazine（25 μ M）心脏迷走神经元在体外没有改变自发活动的神经元或静息膜电位的放电频率，但是，印防己毒素（100 μ M）显着去极化心脏迷走神经元，并增加其发射。同样，gabazine（25 μ M）选择性阻断GABA能IPSC，但不改变心脏迷走神经元的保持电流，而印防己毒素（100 μ M）不仅阻断GABA能IPSC，但也迅速降低紧张性电流。因为紧张性电流可归因于周围GABA对GABA受体的激活，或者可替代地，自发开放组成性活性GABA通道，所以应用GAT-1 GABA转运蛋白NO-711（10 μ M）的拮抗剂来区分这些可能性。NO-711没有显着改变这些神经元的保持电流。苯二氮卓类药物氟硝西泮（1 μ M）显著增加了强直电流和GABA能IPSC衰减时间;然而，令人惊讶的是，在加巴嗪氟硝西泮存在下，未能引起任何变化。这些结果表明，心脏迷走神经元具有介导相位突触电流的GABA（A）受体，这是一种对GABA不敏感但对印防己毒素敏感的突触外强直电流，当阻断时，它会去极化并增加心脏迷走神经元的放电率，而苯二氮卓类药物招募了第三种类型的GABA（A）受体，这种受体对GABA敏感并增强突触外强直电流。
Recent work suggests neurons can have different types of gamma-aminobutyric acid type A (GABA(A)) receptors that mediate phasic inhibitory postsynaptic currents (IPSCs) and tonic currents. This study examines the diversity of GABAergic synaptic currents in parasympathetic cardioinhibitory neurons that receive rhythmic bursts of GABAergic neurotransmission. Focal application of gabazine (25 mu M) to cardiac vagal neurons in vitro did not change the frequency of firing in spontaneously active neurons or the resting membrane potential; however, picrotoxin (100 mu M) significantly depolarized cardiac vagal neurons and increased their firing. Similarly, gabazine (25 mu M) selectively blocked GABAergic IPSCs but did not change holding current in cardiac vagal neurons, whereas picrotoxin (100 mu M) not only blocked GABAergic IPSCs but also rapidly decreased the tonic current. Because the tonic current could be attributable to activation of GABA receptors by ambient GABA or, alternatively, spontaneous opening of constitutively active GABA channels, an antagonist for the GAT-1 GABA transporter NO-711 ( 10 mu M) was applied to distinguish between these possibilities. NO-711 did not significantly alter the holding current in these neurons. The benzodiazepine flunitrazepam (1 mu M) significantly increased the tonic current and GABAergic IPSC decay time; surprisingly, however, in the presence of gabazine flunitrazepam failed to elicit any change. These results suggest cardiac vagal neurons possess gabazine-sensitive GABA(A) receptors that mediate phasic synaptic currents, a gabazine-insensitive but picrotoxin-sensitive extrasynaptic tonic current that when blocked depolarizes and increases the firing rate of cardiac vagal neurons, and benzodiazepines recruit a third type of GABA(A) receptor that is sensitive to gabazine and augments the extrasynaptic tonic current.