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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Modulation of BK channel voltage gating by different auxiliary β subunits
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Modulation of BK channel voltage gating by different auxiliary β subunits

机译：不同辅助β亚基对BK通道电压门控的调制

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摘要

Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming a subunit of BK is associated with one of four alternative ft subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, p1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca~(2+) sensitivity. To determine the extent to which p subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK a subunit alone and with the different β subunits expressed in Xenopus oocytes (β1, β2IR, β3b, and β4). We found that β1, β2, and β4 stabilize the BK voltage sensor in the active conformation. β3 has no effect on voltage sensor equilibrium. In addition, β4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in a β4 channels explains most of their biophysical properties. For channels composed of the a subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K~+ current activation. In the presence of β1, β2, and β4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps.
机译：钙激活和钾激活的钾通道（BK）受多种信号调节。普遍的观点是，不同的BK门控机制会聚在一起以确定通道打开，并且这些门控机制是变构耦合的。在大多数情况下，形成BK亚基的孔与四个替代性ft亚基之一有关，它们似乎靶向特定的门控机制以调节通道活性。特别地，p1稳定了对BK Ca〜（2+）灵敏度具有很大影响的BK电压传感器的有源配置。为了确定p个亚基调节BK电压传感器的程度，我们测量了成孔BK a亚基单独和爪蟾卵母细胞中表达的不同β亚基（β1，β2IR，β3b和β4）诱导的门控电流。我们发现β1，β2和β4使BK电压传感器稳定在活性构象中。 β3对电压传感器平衡没有影响。另外，β4减少了每个电压传感器的视在电荷数量。 β4通道中与电压传感器相关的电荷减少说明了其大部分生物物理特性。对于仅由一个亚基组成的通道，如果电荷的显着部分以与K +电流激活相当的时间进程发展，则选通电荷会随脉冲持续时间缓慢增加。在存在β1，β2和β4的情况下，这种缓慢的成分会比离子电流激活提前发展，并且发展得比离子电流激活快得多，这表明BK通道开放分为两个步骤进行。

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    Gustavo F. Contreras; Alan Neely; Osvaldo Alvarez; Carlos Gonzalez; Ramon Latorre;

  • 作者单位

    Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias,Universidad de Valparaiso, Valparaiso 2366103, Chile,Doctorado en Ciencias mencion Neurociencia, Universidad de Valparaiso, Valparaiso 2366103, Chile;

    Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias,Universidad de Valparaiso, Valparaiso 2366103, Chile;

    Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias,Universidad de Valparaiso, Valparaiso 2366103, Chile,Facultad de Ciencias, Universidad de Chile, Santiago 7800003, Chile;

    Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias,Universidad de Valparaiso, Valparaiso 2366103, Chile;

    Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias,Universidad de Valparaiso, Valparaiso 2366103, Chile;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    kinetic model; modulatory beta subunits;

    机译：动力学模型调节性β亚基;

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