Piskorowski Rebecca, Aldrich Richard W
Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5345, USA.
Nature. 2002 Dec 5;420(6915):499-502. doi: 10.1038/nature01199.
In many physiological systems such as neurotransmitter release, smooth muscle relaxation and frequency tuning of auditory hair cells, large-conductance calcium-activated potassium (BK(Ca)) channels create a connection between calcium signalling pathways and membrane excitability. BK(Ca) channels are activated by voltage and by micromolar concentrations of intracellular calcium. Although it is possible to open BK(Ca) channels in the absence of calcium, calcium binding is essential for their activation under physiological conditions. In the presence of intracellular calcium, BK(Ca) channels open at more negative membrane potentials. Many experiments investigating the molecular mechanism of calcium activation of the BK(Ca) channel have focused on the large intracellular carboxy terminus, and much evidence supports the hypothesis that calcium-binding sites are located in this region of the channel. Here we show that BK(Ca) channels that lack the whole intracellular C terminus retain wild-type calcium sensitivity. These results show that the intracellular C terminus, including the 'calcium bowl' and the RCK domain, is not necessary for the calcium-activated opening of these channels.
在许多生理系统中,如神经递质释放、平滑肌舒张以及听觉毛细胞的频率调谐,大电导钙激活钾(BK(Ca))通道在钙信号通路与膜兴奋性之间建立了联系。BK(Ca)通道可被电压以及微摩尔浓度的细胞内钙激活。尽管在没有钙的情况下也有可能打开BK(Ca)通道,但在生理条件下,钙结合对于其激活至关重要。在存在细胞内钙的情况下,BK(Ca)通道在更负的膜电位时打开。许多研究BK(Ca)通道钙激活分子机制的实验都集中在大的细胞内羧基末端,并且有大量证据支持钙结合位点位于通道这一区域的假说。在此我们表明,缺乏整个细胞内C末端的BK(Ca)通道仍保留野生型钙敏感性。这些结果表明,包括“钙碗”和RCK结构域在内的细胞内C末端对于这些通道的钙激活开放并非必需。