Pharmacological inhibition of cation-chloride cotransporters for neurological diseases

Pharmacological inhibition of cation-chloride

cotransporters for neurological diseases Rachel Nepomuceno;Dandan Sun

【期刊名称】中国神经再生研究（英文版）

【年(卷),期】2015(010)012

【总页数】2

γ-Aminobutyric acid (GABA) is a major neurotransmitter and plays important roles in both the developing and mature central nervous system (CNS). One way that GABA can act is by binding to fast, ionotropic GABAAreceptors in neurons. The binding of GABA to GABAA receptors causes a conformational change that opens ion channels, allowing the passage of Cl–ions. In mature adults, intracellular Cl–concentration ([Cl–]i) is low, and the opening of these ion channels triggers influx of Cl–ions, causing hyperpolarization and neuronal inhibition (Blaesse, 2009). However, in the developing nervous system, [Cl–]iis high, and the binding of GABA to GABAAreceptors induces a depolarizing excitatory response (Figure 1). This leads to the stimulation of voltage-dependent Ca2+channels, which is important for proper neuronal proliferation and differentiation in their circuitry development. Gradual changes in [Cl–]iduring development, known as the “GABA shift”, determine the strength and polarity of GABA-mediated activity. The precise regulation of [Cl–]i is determined by two major cation-