University "Magna Graecia" of Catanzaro, School of Medicine, Science of Health Department , Catanzaro , Italy.
Expert Opin Ther Targets. 2015 Jul;19(7):911-26. doi: 10.1517/14728222.2015.1026258. Epub 2015 Apr 3.
BK (big potassium) channels are Ca(2+)-activated K(+) channels widely expressed in mammalian cells. They are extensively distributed in the CNS, the most abundant level being found in brain areas largely involved in epilepsy, namely cortex, hippocampus, piriform cortex, and other limbic structures. BK channels control action potential shape/duration, thereby regulating membrane excitability and Ca(2+) signaling.
The potassium channel superfamily represents a rich source of potential targets for therapeutic intervention in epilepsy. Some studies have identified alterations in BK channel function, therefore, supporting the development of drugs acting on these channels for epilepsy treatment.
The actual sketch is intriguing and controversial, since mechanisms altering the physiological role of BK channels leading to either a loss- or gain-of-function have both been linked to seizure onset. Not many studies have been performed to unravel the efficacy of drugs acting on these channels as potential antiepileptics; however, paradoxically, efficacy has been demonstrated for both BK channel openers and blockers. Furthermore, their potential usefulness in preventing epileptogenesis has not been investigated at all. Substantial data on risks and benefits of modulating these channels are urgently needed to draw a definitive conclusion on whether BK channels are a viable future target for the treatment of epilepsy.
BK（大钾）通道是一种广泛存在于哺乳动物细胞中的 Ca(2+)激活的 K(+)通道。它们在中枢神经系统中广泛分布，其中含量最丰富的区域是与癫痫密切相关的脑区，包括皮层、海马、梨状皮层和其他边缘结构。BK 通道控制动作电位的形状/持续时间，从而调节膜兴奋性和 Ca(2+)信号。
钾通道超家族是治疗癫痫潜在靶点的丰富来源。一些研究已经确定了 BK 通道功能的改变，因此，开发针对这些通道的药物用于癫痫治疗具有一定的发展潜力。
实际情况既有趣又有争议，因为改变 BK 通道生理作用的机制，无论是导致功能丧失还是功能获得，都与癫痫发作有关。尽管已经进行了一些研究来阐明作用于这些通道的药物作为潜在抗癫痫药的疗效，但矛盾的是，BK 通道开放剂和阻滞剂都显示出了疗效。此外，它们在预防癫痫发生方面的潜在用途根本没有被研究过。迫切需要大量关于调节这些通道的风险和益处的数据，以便就 BK 通道是否是治疗癫痫的可行未来靶点得出明确的结论。
