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大电导钙激活钾通道β2亚基的运作模式。

Modes of operation of the BKCa channel beta2 subunit.

作者信息

Savalli Nicoletta, Kondratiev Andrei, de Quintana Sarah Buxton, Toro Ligia, Olcese Riccardo

机构信息

Department of Anesthesiology-Division of Molecular Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA.

出版信息

J Gen Physiol. 2007 Jul;130(1):117-31. doi: 10.1085/jgp.200709803.

DOI:10.1085/jgp.200709803
PMID:17591990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2154362/
Abstract

The beta(2) subunit of the large conductance Ca(2+)- and voltage-activated K(+) channel (BK(Ca)) modulates a number of channel functions, such as the apparent Ca(2+)/voltage sensitivity, pharmacological and kinetic properties of the channel. In addition, the N terminus of the beta(2) subunit acts as an inactivating particle that produces a relatively fast inactivation of the ionic conductance. Applying voltage clamp fluorometry to fluorescently labeled human BK(Ca) channels (hSlo), we have investigated the mechanisms of operation of the beta(2) subunit. We found that the leftward shift on the voltage axis of channel activation curves (G(V)) produced by coexpression with beta(2) subunits is associated with a shift in the same direction of the fluorescence vs. voltage curves (F(V)), which are reporting the voltage dependence of the main voltage-sensing region of hSlo (S4-transmembrane domain). In addition, we investigated the inactivating mechanism of the beta(2) subunits by comparing its properties with the ones of the typical N-type inactivation process of Shaker channel. While fluorescence recordings from the inactivated Shaker channels revealed the immobilization of the S4 segments in the active conformation, we did not observe a similar feature in BK(Ca) channels coexpressed with the beta(2) subunit. The experimental observations are consistent with the view that the beta(2) subunit of BK(Ca) channels facilitates channel activation by changing the voltage sensor equilibrium and that the beta(2)-induced inactivation process does not follow a typical N-type mechanism.

摘要

大电导钙（2+）和电压激活钾（+）通道（BK（Ca））的β（2）亚基调节多种通道功能，如通道的表观钙（2+）/电压敏感性、药理学和动力学特性。此外，β（2）亚基的N端作为一个失活颗粒，可使离子电导产生相对快速的失活。通过对荧光标记的人BK（Ca）通道（hSlo）应用电压钳荧光法，我们研究了β（2）亚基的作用机制。我们发现，与β（2）亚基共表达所导致的通道激活曲线（G（V））在电压轴上的左移，与荧光-电压曲线（F（V））在相同方向上的移动相关，F（V）曲线反映了hSlo主要电压感应区域（S4跨膜结构域）的电压依赖性。此外，我们通过将β（2）亚基的特性与Shaker通道典型N型失活过程的特性进行比较，研究了β（2）亚基的失活机制。虽然失活的Shaker通道的荧光记录显示S4片段固定在活性构象中，但在与β（2）亚基共表达的BK（Ca）通道中我们未观察到类似特征。这些实验观察结果与以下观点一致：BK（Ca）通道的β（2）亚基通过改变电压传感器平衡促进通道激活，且β（2）诱导的失活过程不遵循典型的N型机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/deac2487dc8f/jgp1300117f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/6ffdffce452c/jgp1300117f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/f61b96a3bae5/jgp1300117f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/3a8414c80fa2/jgp1300117f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/f5f111f97b81/jgp1300117f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/38b43a121ba0/jgp1300117f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/d0d6065ef9cb/jgp1300117f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/53d8f1a33d73/jgp1300117f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/ec84ca54f91f/jgp1300117f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/bf11971c6a3f/jgp1300117f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/deac2487dc8f/jgp1300117f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/6ffdffce452c/jgp1300117f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/f61b96a3bae5/jgp1300117f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/3a8414c80fa2/jgp1300117f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/f5f111f97b81/jgp1300117f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/38b43a121ba0/jgp1300117f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/d0d6065ef9cb/jgp1300117f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/53d8f1a33d73/jgp1300117f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/ec84ca54f91f/jgp1300117f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/bf11971c6a3f/jgp1300117f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93b9/2154362/deac2487dc8f/jgp1300117f10.jpg

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