Shenoda Botros
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop #488, Philadelphia, PA, 19102, USA,
Transl Stroke Res. 2015 Jun;6(3):181-90. doi: 10.1007/s12975-015-0395-9. Epub 2015 Apr 11.
The Na(+)/Ca(2+) exchanger (NCX) plays an important role in the maintenance of Na(+) and Ca(2+) homeostasis in most cells including neurons under physiological and pathological conditions. It exists in three subtypes (NCX1-3) with different tissue distributions but all of them are present in the brain. NCX transports Na(+) and Ca(2+) in either Ca(2+)-efflux (forward) or Ca(2+)-influx (reverse) mode, depending on membrane potential and transmembrane ion gradients. During neuronal ischemia, Na(+) and Ca(2+) ionic disturbances favor NCX to work in reverse mode, giving rise to increased intracellular Ca(2+) levels, while it may regain its forward mode activity on reperfusion. The exact significance of NCX in neuronal ischemic and reperfusion states remains unclear. The differential role of NCX subtypes in ischemic neuronal injury has been extensively investigated using various pharmacological tools as well as genetic models. This review discusses the mode of action of NCX in ischemic and reperfusion states, the differential roles played by NCX subtypes in these states as well as the role of NCX in pre- and postconditioning. NCX subtypes carry variable roles in ischemic injury. Furthermore, the mode of action of each subtype varies in ischemia and reperfusion states. Thus, therapeutic targeting of NCX in stroke should be based on appropriate timing of the administration of NCX subtype-specific strategies.
钠钙交换体（NCX）在包括神经元在内的大多数细胞维持生理和病理条件下的钠（Na⁺）和钙（Ca²⁺）稳态方面发挥着重要作用。它以三种亚型（NCX1 - 3）存在，具有不同的组织分布，但它们都存在于大脑中。NCX根据膜电位和跨膜离子梯度，以钙外流（正向）或钙内流（反向）模式转运Na⁺和Ca²⁺。在神经元缺血期间，Na⁺和Ca²⁺离子紊乱有利于NCX以反向模式工作，导致细胞内Ca²⁺水平升高，而在再灌注时它可能恢复其正向模式活性。NCX在神经元缺血和再灌注状态的确切意义仍不清楚。使用各种药理学工具以及基因模型对NCX亚型在缺血性神经元损伤中的不同作用进行了广泛研究。本综述讨论了NCX在缺血和再灌注状态下的作用模式、NCX亚型在这些状态中所起的不同作用以及NCX在预处理和后处理中的作用。NCX亚型在缺血性损伤中发挥着不同的作用。此外，每种亚型的作用模式在缺血和再灌注状态下有所不同。因此，针对中风的NCX治疗靶点应基于NCX亚型特异性策略给药的适当时间。
