Kiss L, Korn S J
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269, USA.
Biophys J. 1998 Apr;74(4):1840-9. doi: 10.1016/S0006-3495(98)77894-4.
With prolonged or repetitive activation, voltage-gated K+ channels undergo a slow (C-type) inactivation mechanism, which decreases current flow through the channel. Previous observations suggest that C-type inactivation results from a localized constriction in the outer mouth of the channel pore and that the rate of inactivation is controlled by the-rate at which K+ leaves an unidentified binding site in the pore. We have functionally identified two K+ binding sites in the conduction pathway of a chimeric K+ channel that conducts Na+ in the absence of K+. One site has a high affinity for K+ and contributes to the selectivity filter mechanism for K+ over Na+. Another site, external to the high-affinity site, has a lower affinity for K+ and is not involved in channel selectivity. Binding of K+ to the high-affinity binding site slowed inactivation. Binding of cations to the external low-affinity site did not slow inactivation directly but could slow it indirectly, apparently by trapping K+ at the high-affinity site. These data support a model whereby C-type inactivation involves a constriction at the selectivity filter, and the constriction cannot proceed when the selectivity filter is occupied by K+.
随着长时间或重复性激活，电压门控钾离子通道会经历一种缓慢的（C型）失活机制，这种机制会减少通过该通道的电流。先前的观察结果表明，C型失活是由通道孔外口的局部收缩引起的，并且失活速率由钾离子离开孔中一个未明确的结合位点的速率控制。我们在一个嵌合钾离子通道的传导途径中功能性地鉴定出了两个钾离子结合位点，该嵌合钾离子通道在没有钾离子的情况下传导钠离子。一个位点对钾离子具有高亲和力，并有助于钾离子相对于钠离子的选择性过滤机制。另一个位点位于高亲和力位点之外，对钾离子的亲和力较低，且不参与通道选择性。钾离子与高亲和力结合位点的结合减缓了失活。阳离子与外部低亲和力位点的结合不会直接减缓失活，但可能会间接减缓失活，显然是通过将钾离子捕获在高亲和力位点上。这些数据支持了一种模型，即C型失活涉及选择性过滤器处的收缩，并且当选择性过滤器被钾离子占据时，收缩无法进行。
