Programmed cell death or apoptosis is broadly responsible for the normal homeostatic removal of cells and has been increasingly implicated in mediating pathological cell loss in many disease states. As the molecular mechanisms of apoptosis have been extensively investigated a critical role for ionic homeostasis in apoptosis has been recently endorsed. In contrast to the ionic mechanism of necrosis that involves Ca(2+) influx and intracellular Ca(2+) accumulation, compelling evidence now indicates that excessive K(+) efflux and intracellular K(+) depletion are key early steps in apoptosis. Physiological concentration of intracellular K(+) acts as a repressor of apoptotic effectors. A huge loss of cellular K(+), likely a common event in apoptosis of many cell types, may serve as a disaster signal allowing the execution of the suicide program by activating key events in the apoptotic cascade including caspase cleavage, cytochrome c release, and endonuclease activation. The pro-apoptotic disruption of K(+) homeostasis can be mediated by over-activated K(+) channels or ionotropic glutamate receptor channels, and most likely, accompanied by reduced K(+) uptake due to dysfunction of Na(+), K(+)-ATPase. Recent studies indicate that, in addition to the K(+) channels in the plasma membrane, mitochondrial K(+) channels and K(+) homeostasis also play important roles in apoptosis. Investigations on the K(+) regulation of apoptosis have provided a more comprehensive understanding of the apoptotic mechanism and may afford novel therapeutic strategies for apoptosis-related diseases.

中文翻译：

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钾稳态在细胞凋亡中的调控及其关键作用。

程序性细胞死亡或编程性细胞死亡广泛负责正常的稳态细胞去除，并在许多疾病状态下越来越多地参与介导病理性细胞丢失。由于已经广泛研究了细胞凋亡的分子机制，所以最近已经认可了离子稳态在细胞凋亡中的关键作用。与涉及Ca（2+）涌入和细胞内Ca（2+）积累的坏死的离子机制相反，有力的证据表明，过量的K（+）外排和细胞内K（+）消耗是凋亡中的关键早期步骤。细胞内K（+）的生理浓度充当细胞凋亡效应因子的阻遏物。细胞K（+）的大量损失，可能是许多细胞类型凋亡中的常见事件，可能通过激活凋亡级联反应中的关键事件（包括胱天蛋白酶裂解，细胞色素C释放和核酸内切酶激活）来执行自杀程序，成为灾难信号。K（+）动态平衡的促凋亡破坏可以由过度激活的K（+）通道或离子型谷氨酸受体通道介导，最有可能伴随着由于Na（+）功能异常而导致K（+）吸收减少， K（+）-ATPase。最近的研究表明，除了质膜中的K（+）通道外，线粒体K（+）通道和K（+）稳态在凋亡中也起着重要作用。对细胞凋亡的K（+）调控的研究已提供了对凋亡机制的更全面的了解，并可能为凋亡相关疾病提供新的治疗策略。