Medical Scientist Training Program and Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University Boston, MA, USA.
Department of Neuroscience, Tufts University School of Medicine Boston, MA, USA.
Front Neural Circuits. 2014 Feb 3;8:3. doi: 10.3389/fncir.2014.00003. eCollection 2014.
The diversity of GABAA receptor (GABAAR) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Phasic inhibition is mediated by synaptically-localized receptors with a low affinity for GABA and results in a transient, rapidly desensitizing GABAergic conductance; whereas, tonic inhibition is mediated by extrasynaptic receptors with a high affinity for GABA and results in a persistent GABAergic conductance. The specific functions of tonic versus phasic GABAergic inhibition in different cell types and the impact on specific neural circuits are only beginning to be unraveled. Here we review the diversity in the magnitude of tonic GABAergic inhibition in various brain regions and cell types, and highlight the impact on neuronal excitability in different neuronal circuits. Further, we discuss the relevance of tonic inhibition in various physiological and pathological contexts as well as the potential of targeting these receptor subtypes for treatment of diseases, such as epilepsy.
GABAA 受体 (GABAAR) 亚基的多样性和亚基组装过程中的众多构象导致了具有不同功能特性的各种受体。这种异质性导致了许多脑区和细胞类型中 GABA 能电导的变化。突触定位的受体对 GABA 的亲和力低，介导阶段性抑制，导致 GABA 能电导的短暂、快速脱敏；而 GABA 亲和力高的突触外受体介导紧张性抑制，导致持续的 GABA 能电导。在不同的细胞类型中，紧张性与阶段性 GABA 能抑制的特定功能以及对特定神经回路的影响才刚刚开始被揭示。在这里，我们回顾了不同脑区和细胞类型中紧张性 GABA 能抑制的幅度的多样性，并强调了其对不同神经元回路中神经元兴奋性的影响。此外，我们还讨论了紧张性抑制在各种生理和病理情况下的相关性，以及针对这些受体亚型治疗疾病（如癫痫）的潜力。
