Membrane depolarization activates BK channels through ROCK-mediated β1 subunit surface trafficking to limit vasoconstriction.
Membrane depolarization activates BK channels through ROCK-mediated β1 subunit surface trafficking to limit vasoconstriction.
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DOI：
10.1126/scisignal.aah5417
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发表时间：
2017-05-09
影响因子：
7.3
通讯作者：
Jaggar JH
中科院分区：
文献类型：
--
作者：
Leo MD;Zhai X;Muralidharan P;Kuruvilla KP;Bulley S;Boop FA;Jaggar JH
调节局部器官血流的小动脉中平滑肌细胞（肌细胞）的膜去极化导致血管收缩。膜去极化也激活大电导钙（Ca2+）活化钾（BK）通道，这限制了促进血管收缩的Ca2+通道活性，从而导致血管舒张。我们发现，在人和大鼠动脉肌细胞中，膜去极化迅速增加了细胞表面辅助性BK β1亚基的丰度，但没有增加形成孔的BKα通道的丰度。膜去极化刺激电压依赖性Ca2+通道，导致Ca2+内流和Rho激酶（ROCK） 1和2的激活。rock1 /2介导的Rab11A活化促进了β1亚基通过Rab11A阳性循环内体传递到质膜。这些额外的β1亚基与已经在质膜上的BKα通道相关，导致Ca2+明显敏感性的增加和加压动脉肌细胞通道的激活和血管舒张。因此，膜去极化通过刺激ROCK-和rab11a依赖性β1亚基向动脉肌细胞表面的转运来激活BK通道。
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca2+)–activated potassium (BK) channels, which limits Ca2+ channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels. Membrane depolarization stimulated voltage-dependent Ca2+ channels, leading to Ca2+ influx and the activation of Rho kinase (ROCK) 1 and 2. ROCK1/2-mediated activation of Rab11A promoted the delivery of β1 subunits to the plasma membrane by Rab11A-positive recycling endosomes. These additional β1 subunits associated with BKα channels already at the plasma membrane, leading to an increase in apparent Ca2+ sensitivity and activation of the channels in pressurized arterial myocytes and vasodilation. Thus, membrane depolarization activates BK channels through stimulation of ROCK- and Rab11A-dependent trafficking of β1 subunits to the surface of arterial myocytes.
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影响因子：
56.9
作者：
NELSON, MT;CHENG, H;LEDERER, WJ
通讯作者：
LEDERER, WJ
DOI：
10.1152/nips.01387.2002
发表时间：
2002-08-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Orio, P;Rojas, P;Latorre, R
通讯作者：
Latorre, R
DOI：
10.1073/pnas.1317527111
发表时间：
2014-02-11
影响因子：
11.1
作者：
Leo, M. Dennis;Bannister, John P.;Jaggar, Jonathan H.
通讯作者：
Jaggar, Jonathan H.
DOI：
10.1085/jgp.116.3.411
发表时间：
2000-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cox DH;Aldrich RW
通讯作者：
Aldrich RW
DOI：
10.1152/ajpcell.2001.281.2.c439
发表时间：
2001-08-01
影响因子：
5.5
作者：
Jaggar, JH
通讯作者：
Jaggar, JH