Functional consequences of a decreased potassium affinity in a potassium channel pore. Ion interactions and C-type inactivation.
Functional consequences of a decreased potassium affinity in a potassium channel pore. Ion interactions and C-type inactivation.
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DOI：
10.1085/jgp.113.2.347
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发表时间：
1999-02
期刊：
影响因子：
--
通讯作者：
Aldrich RW
中科院分区：
文献类型：
--
作者：
Ogielska EM;Aldrich RW
钾通道孔外口附近结合的离子阻碍了 C 型失活构象变化（Lopez-Barneo, J., T. Hoshi, S. Heinemann, and R. Aldrich. 1993. Receptors Channels. 1:61–71; Baukrowitz, T., and G. Yellen. 1995. Neuron. 15:951-960）。在这项研究中，我们提出的证据表明，渗透离子对 C 型失活调节位点的占据不仅取决于其内在亲和力，而且也是钾通道孔中相邻位点的相对亲和力的函数。 Shaker S6 区域的 A463C 突变降低了孔中内部离子结合位点的亲和力（Ogielska, E.M. 和 R.W. Aldrich, 1998）。然而，我们发现这种突变也降低了通道的C型失活率。我们的研究表明，在 A463 位点取代时观察到的 C 型失活效应最有可能是由于通道的孔占用率的变化，而不是 C 型失活构象变化的变化。我们发现孔中内部离子结合位点的钾亲和力降低会导致孔中离子之间的（静电）相互作用降低，从而延长离子在外部 C 型失活位点上保持结合的时间。我们还提供了证据，表明 C 型失活收缩是相当局部的，并且不涉及选择性过滤器的全面崩溃。我们的数据表明，在 A463C 中，钾可以结合在选择性过滤器内，而不干扰 C 型失活过程。
Ions bound near the external mouth of the potassium channel pore impede the C-type inactivation conformational change (Lopez-Barneo, J., T. Hoshi, S. Heinemann, and R. Aldrich. 1993. Receptors Channels. 1:61– 71; Baukrowitz, T., and G. Yellen. 1995. Neuron. 15:951–960). In this study, we present evidence that the occupancy of the C-type inactivation modulatory site by permeant ions is not solely dependent on its intrinsic affinity, but is also a function of the relative affinities of the neighboring sites in the potassium channel pore. The A463C mutation in the S6 region of Shaker decreases the affinity of an internal ion binding site in the pore (Ogielska, E.M., and R.W. Aldrich, 1998). However, we have found that this mutation also decreases the C-type inactivation rate of the channel. Our studies indicate that the C-type inactivation effects observed with substitutions at position A463 most likely result from changes in the pore occupancy of the channel, rather than a change in the C-type inactivation conformational change. We have found that a decrease in the potassium affinity of the internal ion binding site in the pore results in lowered (electrostatic) interactions among ions in the pore and as a result prolongs the time an ion remains bound at the external C-type inactivation site. We also present evidence that the C-type inactivation constriction is quite local and does not involve a general collapse of the selectivity filter. Our data indicate that in A463C potassium can bind within the selectivity filter without interfering with the process of C-type inactivation.
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DOI：
10.1085/jgp.111.2.195
发表时间：
1998-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Kiss L;Immke D;LoTurco J;Korn SJ
通讯作者：
Korn SJ
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.4
作者：
Ogielska, EM;Zagotta, WN;Aldrich, RW
通讯作者：
Aldrich, RW
离子通过C型灭活振荡器通道传导。
影响因子：
3.8
作者：
Starkus, JG;Kuschel, L;Rayner, MD;Heinemann, SH
通讯作者：
Heinemann, SH
影响因子：
56.9
作者：
Baukrowitz, T;Yellen, G
通讯作者：
Yellen, G