Graduate Program in Physiology, Biophysics and Systems Biology, Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA.
Channels (Austin). 2011 May-Jun;5(3):269-79. doi: 10.4161/chan.5.3.15827. Epub 2011 May 1.
The inwardly rectifying potassium channel (Kir), Kir4.1 mediates spatial K(+)-buffering in the CNS. In this process the channel is potentially exposed to a large range of extracellular K(+) concentrations ([K(+)]o). We found that Kir4.1 is regulated by K(+)o. Increased [K(+)]o leads to a slow (mins) increase in the whole-cell currents of Xenopus oocytes expressing Kir4.1. Conversely, removing K(+) from the bath solution results in a slow decrease of the currents. This regulation is not coupled to the pHi-sensitive gate of the channel, nor does it require the presence of K67, a residue necessary for K(+)o-dependent regulation of Kir1.1. The voltage-dependent blockers Cs(+) and Ba(2+) substitute for K(+) and prevent deactivation of the channel in the absence of K(+)o. Cs(+) blocks and regulates the channel with similar affinity, consistent with the regulatory sites being in the selectivity-filter of the channel. Although both Rb(+) and NH4(+) permeate Kir4.1, only Rb(+) is able to regulate the channel. We conclude that Kir4.1 is regulated by ions interacting with specific sites in the selectivity filter. Using a kinetic model of the permeation process we show the plausibility of the channel's sensing the extracellular ionic environment through changes in the selectivity occupancy pattern, and that it is feasible for an ion with the selectivity properties of NH4(+) to permeate the channel without inducing these changes.
内向整流钾通道（Kir），Kir4.1 介导中枢神经系统中的空间 K（+）缓冲。在此过程中，通道可能会暴露于大范围的细胞外 K（+）浓度（[K（+）]o）。我们发现 Kir4.1 受到 K（+）o 的调节。增加[K（+）]o 会导致表达 Kir4.1 的非洲爪蟾卵母细胞的全细胞电流缓慢（分钟）增加。相反，从浴液中去除 K（+）会导致电流缓慢下降。这种调节与通道的 pH 敏感门无关，也不需要 K67，K67 是 Kir1.1 依赖 K（+）o 调节所必需的残基。电压依赖性阻断剂 Cs（+）和 Ba（2+）替代 K（+），并防止在没有 K（+）o 的情况下通道失活。Cs（+）以相似的亲和力阻断和调节通道，这与调节位点位于通道的选择性滤器中一致。虽然 Rb（+）和 NH4（+）都能渗透 Kir4.1，但只有 Rb（+）能够调节通道。我们得出结论，Kir4.1 受到与选择性滤器中特定位点相互作用的离子的调节。通过渗透过程的动力学模型，我们表明通道通过改变选择性占据模式来感知细胞外离子环境的可能性，并且对于具有 NH4（+）选择性特性的离子来说，在不引起这些变化的情况下渗透通道是可行的。
