Dual GABAA receptor-mediated inhibition in rat presympathetic paraventricular nucleus neurons
Dual GABAA receptor-mediated inhibition in rat presympathetic paraventricular nucleus neurons
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DOI：
10.1113/jphysiol.2007.133223
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发表时间：
2007-07-15
影响因子：
5.5
通讯作者：
Stern, Javier E.
中科院分区：
文献类型：
--
作者：
Park, Jin Bong;Skalska, Silvia;Stern, Javier E.
抑制性神经递质GABA在室旁核神经元兴奋性和交感神经兴奋性流出的调节中起着重要作用。除了介导常规的突触传递（阶段性抑制）之外，最近发现具有不同生物物理、分子和药理学特性的GABA（A）受体是较慢的、持久的抑制形式（强直性抑制）的基础。无论是'紧张'抑制方式存在于前交感PVN神经元，它的作用是在调制其活动是目前未知的。在这里，我们将神经束追踪技术与膜片钳电生理学相结合来解决这些问题。从PVN-RVLM（延髓头端腹外侧）投射神经元获得的记录显示，除了阻断GABA（A）介导的抑制性突触后电流（IPSC，I相）外，GABA（A）受体阻断剂荷包牡丹碱和印防己毒素引起保持电流（I-紧张性）的向外偏移。相反，高亲和力GABA（A）阻断剂gabazine阻断I相而不影响I紧张性。THIP是一种GABA（A）受体激动剂，它优先激活δ-受体而不是γ-受体，增强了I-紧张的幅度。我们的研究结果还表明，在强烈和/或同步的突触活动的条件下，I-紧张可能被激活的溢出的突触释放的GABA。阻断I-tonic诱导PVN-RVLM神经元膜去极化，增加放电活动，增强PVN-RVLM神经元的输入输出功能。总之，我们的研究结果支持存在持续的GABA（A）介导的抑制方式在前交感PVN神经元，这在调节其兴奋性和放电活动中起着重要作用。
The inhibitory neurotransmitter GABA plays a key role in the modulation of paraventricular nucleus (PVN) neuronal excitability and sympathoexcitatory outflow, under both physiological and pathological conditions. In addition to mediating conventional synaptic transmission (phasic inhibition), GABA(A) receptors of distinct biophysical, molecular and pharmacological properties have been recently found to underlie a slower, persistent form of inhibition (tonic inhibition). Whether the 'tonic' inhibitory modality is present in presympathetic PVN neurons, and what its role is in modulating their activity is at present unknown. Here, we combined tract-tracing techniques with patch-clamp electrophysiology to address these questions. Recordings obtained from PVN-RVLM (rostral ventrolateral medulla) projecting neurons show that besides blocking GABA(A)-mediated inhibitory postsynaptic currents (IPSCs, I-phasic), the GABA(A) receptor blockers bicuculline and picrotoxin caused an outward shift in the holding current (I-tonic). Conversely, the high affinity GABA(A) blocker gabazine blocked I-phasic without affecting I-tonic. THIP, a GABA(A) receptor agonist that preferentially activates delta- over gamma-containing receptors, enhanced the magnitude of I-tonic. Our results also indicate that during conditions of strong and/or synchronous synaptic activity, I-tonic may be activated by spillover of synaptically released GABA. Blockade of I-tonic induced membrane depolarization, increased firing activity, and enhanced the input-output function of PVN-RVLM neurons. Altogether, our results support the presence of a persistent GABA(A)-mediated inhibitory modality in presympathetic PVN neurons, which plays a major role in modulating their excitability and firing activity.