Baukrowitz T, Yellen G
Department of Neurobiology, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Neuron. 1995 Oct;15(4):951-60. doi: 10.1016/0896-6273(95)90185-x.
Voltage-activated K+ currents and their inactivation properties are important for controlling frequency-dependent signaling in neurons and other excitable cells. Two distinct molecular mechanisms for K+ channel inactivation have been described: N-type, which involves rapid occlusion of the open channel by an intracellular tethered blocker, and C-type, which involves a slower change at the extracellular mouth of the pore. We find that frequency-dependent cumulative inactivation of Shaker channels is very sensitive to changes of extracellular [K+] in the physiological range, with much more inactivation at low [K+]out, and that it results from the interaction of N- and C-type inactivation. N-type inactivation enhances C-type inactivation by two mechanisms. First, it inhibits outward K+ flux, which normally fills an external ion site and thus prevents C-type inactivation. Second, it keeps the channel's activation gate open even after repolarization, allowing C-type inactivation to occur for a prolonged period.
电压门控钾离子电流及其失活特性对于控制神经元和其他可兴奋细胞中频率依赖性信号传导至关重要。已经描述了两种不同的钾离子通道失活分子机制：N型，涉及细胞内拴系阻滞剂对开放通道的快速阻塞；C型，涉及孔道细胞外口处较慢的变化。我们发现，Shaker通道的频率依赖性累积失活对生理范围内细胞外[K+]的变化非常敏感，在低[K+]out时失活更多，并且它是由N型和C型失活的相互作用导致的。N型失活通过两种机制增强C型失活。首先，它抑制外向钾离子通量，外向钾离子通量通常会填充外部离子位点，从而防止C型失活。其次，即使在复极化后，它也会使通道的激活门保持打开状态，使C型失活能够持续较长时间。
