Two distinct effects of PIP2 underlie auxiliary subunit-dependent modulation of Slo1 BK channels.
Two distinct effects of PIP2 underlie auxiliary subunit-dependent modulation of Slo1 BK channels.
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DOI：
10.1085/jgp.201511363
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Hoshi T
中科院分区：
文献类型：
--
作者：
Tian Y;Ullrich F;Xu R;Heinemann SH;Hou S;Hoshi T
PIP 2对Slo 1 BK通道的作用依赖于亚基组成。磷脂酰肌醇4，5-二磷酸（PIP 2）在调节许多离子通道的功能中起关键作用，包括大电导Ca 2+和电压依赖性K+（BK，Slo 1）通道。Slo 1 BK通道复合物包括四个成孔Slo 1（α）亚基以及在不同组织中表达的各种调节辅助亚基（β和γ）。我们研究了脑源性PIP 2对人Slo 1 BK通道复合物的影响的分子和生物物理机制，该复合物具有在人胚肾细胞中异源表达的不同亚基组成。PIP 2抑制通过Slo 1通道（无辅助亚基）和Slo 1 + γ1复合物的宏观电流。相反，PIP 2显著增加通过Slo 1 + β1和Slo 1 + β4通道复合物的宏观电流，并且不能改变通过Slo 1 + β2和Slo 1 + β2 Δ2-19通道复合物的宏观电流。在各种膜电位和二价阳离子浓度下获得的结果表明，PIP 2促进所有通道类型中的离子传导门的打开，而不管特定的亚基组合物。然而，在缺乏位于电压传感器结构域（VSD）附近的β亚基的情况下，如Slo 1和可能的Slo 1 + γ1，PIP 2增加了膜细胞质侧的负表面电荷，从而使VSD介导的激活的电压依赖性向正方向移动。当β1或β4亚基占据VSD周围的空间时，只有PIP 2的刺激作用是明显的。天然Slo 1 BK通道的亚基组成在各种细胞类型中不同;因此，PIP 2可以发挥不同的组织和二价阳离子依赖性调节作用。
The effects of PIP2 on Slo1 BK channels depend on subunit composition. Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a critical role in modulating the function of numerous ion channels, including large-conductance Ca2+- and voltage-dependent K+ (BK, Slo1) channels. Slo1 BK channel complexes include four pore-forming Slo1 (α) subunits as well as various regulatory auxiliary subunits (β and γ) that are expressed in different tissues. We examined the molecular and biophysical mechanisms underlying the effects of brain-derived PIP2 on human Slo1 BK channel complexes with different subunit compositions that were heterologously expressed in human embryonic kidney cells. PIP2 inhibited macroscopic currents through Slo1 channels without auxiliary subunits and through Slo1 + γ1 complexes. In contrast, PIP2 markedly increased macroscopic currents through Slo1 + β1 and Slo1 + β4 channel complexes and failed to alter macroscopic currents through Slo1 + β2 and Slo1 + β2 Δ2–19 channel complexes. Results obtained at various membrane potentials and divalent cation concentrations suggest that PIP2 promotes opening of the ion conduction gate in all channel types, regardless of the specific subunit composition. However, in the absence of β subunits positioned near the voltage-sensor domains (VSDs), as in Slo1 and probably Slo1 + γ1, PIP2 augments the negative surface charge on the cytoplasmic side of the membrane, thereby shifting the voltage dependence of VSD-mediated activation in the positive direction. When β1 or β4 subunits occupy the space surrounding the VSDs, only the stimulatory effect of PIP2 is evident. The subunit compositions of native Slo1 BK channels differ in various cell types; thus, PIP2 may exert distinct tissue- and divalent cation–dependent modulatory influences.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1074/jbc.m110.214650
发表时间：
2011-04-29
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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DOI：
10.1085/jgp.201411337
发表时间：
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期刊：
The Journal of general physiology
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1221997110
发表时间：
2013-03-19
影响因子：
11.1
作者：
Hoshi, Toshinori;Wissuwa, Bianka;Hou, Shangwei
通讯作者：
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