Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan, ROC.
Life Sci. 2010 May 22;86(21-22):775-80. doi: 10.1016/j.lfs.2010.04.004. Epub 2010 Apr 10.
A manifestation in neurodegeneration is apoptosis of neurons. Neurons undergoing apoptosis may lose a substantial amount of cytosolic K+ through a number of pathways including K+ efflux via voltage-gated K+ (Kv) channels. The consequent drop in cytosolic [K+] relieves inhibition of an array of pro-apoptotic enzymes such as caspases and nucleases. Blocking Kv channels has been known to prevent neuronal apoptosis by preventing K+ efflux. Some neural diseases such as epilepsy are caused by neuronal hyperexcitability, which eventually may lead to neuronal apoptosis. Reduction in activities of A-type Kv channels and Kv7 subfamily members is amongst the etiological causes of neuronal hyperexcitation; enhancing the opening of these channels may offer opportunities of remedy. This review discusses the potential uses of Kv channel modulators as neuroprotective drugs.
神经退行性变的表现之一是神经元凋亡。通过多种途径，包括通过电压门控钾 (Kv) 通道的钾外流，经历凋亡的神经元可能会失去大量胞质 K+。胞质 [K+] 的随之下降会解除对一系列促凋亡酶（如半胱天冬酶和核酸酶）的抑制。已知阻断 Kv 通道可通过防止 K+外流来防止神经元凋亡。一些神经疾病，如癫痫，是由神经元过度兴奋引起的，最终可能导致神经元凋亡。A型 Kv 通道和 Kv7 亚家族成员活性的降低是神经元过度兴奋的病因之一；增强这些通道的开放可能提供补救的机会。这篇综述讨论了 Kv 通道调节剂作为神经保护药物的潜在用途。
