Cloning and functional characterization of novel large conductance calcium-activated potassium channel β subunits, hKCNMB3 and hKCNMB4
Cloning and functional characterization of novel large conductance calcium-activated potassium channel β subunits, hKCNMB3 and hKCNMB4
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DOI：
10.1074/jbc.275.9.6453
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发表时间：
2000-03-03
影响因子：
4.8
通讯作者：
Aldrich, RW
中科院分区：
文献类型：
--
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
我们克隆和鉴定了两个新的钙激活钾通道β亚基，hKCNMB3和hKCNMB4，它们分别在睾丸和脑中丰富。我们将这些β亚基与先前克隆的小鼠β1亚基(MKCNMB1)和人β2亚基(HKCNMB2)的稳态和动力学特性进行了比较和对比。一旦失活被去除，我们发现hKCNMB2具有类似于mHCNMB1的性质，hKCNMB2减缓了Hslo1通道选通，并将电流-电压关系移动到更负的电位。HKCNMB3和hKCNMB4对mKCNMB1和hKCNMB2未观察到的SLO电流有明显影响。虽然我们发现hHCNMB3确实与Hslo通道相互作用，但它对Hslo1通道的影响很小，增加了Hslo1的激动率，相反，hKCNMB4减缓了Hslo1的门控动力学，并调节了Hslo1的表观钙敏感性。我们发现，β亚基对某些Hslo1通道特性的不同影响是依赖于钙的。MKCNMB1和hKCNMB2在1 mU M时激活缓慢，而在10 mM游离钙浓度下不激活。HKCNMB4在低钙浓度时减少Hslo1通道的开放，但在高钙浓度时增加通道开放。这些结果表明，不同组织类型中的β亚基根据特定细胞的需要微调SLO通道特性。
We present the cloning and characterization of two novel calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4, that are enriched in the testis and brain, respectively. We compare and contrast the steady state and kinetic properties of these beta subunits with the previously cloned mouse beta 1 (mKCNMB1) and the human beta 2 subunit (hKCNMB2). Once inactivation is removed, we find that hKCNMB2 has properties similar to mHCNMB1, hKCNMB2 slows Hslo1 channel gating and shifts the current-voltage relationship to more negative potentials. hKCNMB3 and hKCNMB4 have distinct effects on slo currents not observed with mKCNMB1 and hKCNMB2. Although we found that hHCNMB3 does interact with Hslo channels, its effects on Hslo1 channel properties were slight, increasing Hslo1 activation rates, In contrast, hKCNMB4 slows Hslo1 gating kinetics, and modulates the apparent calcium sensitivity of Hslo1. We found that the different effects of the beta subunits on some Hslo1 channel properties are calcium-dependent. mKCNMB1 and hKCNMB2 slow activation at 1 mu M but not at 10 mu M free calcium concentrations. hKCNMB4 decreases Hslo1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. These results suggest that beta subunits in diverse tissue types fine-tune slo channel properties to the needs of a particular cell.