Zeng X H, Ding J P, Xia X M, Lingle C J
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Gen Physiol. 2001 Jun;117(6):607-28. doi: 10.1085/jgp.117.6.607.
Both beta1 and beta2 auxiliary subunits of the BK-type K(+) channel family profoundly regulate the apparent Ca(2)+ sensitivity of BK-type Ca(2)+-activated K(+) channels. Each produces a pronounced leftward shift in the voltage of half-activation (V(0.5)) at a given Ca(2)+ concentration, particularly at Ca(2)+ above 1 microM. In contrast, the rapidly inactivating beta3b auxiliary produces a leftward shift in activation at Ca(2)+ below 1 microM. In the companion work (Lingle, C.J., X.-H. Zeng, J.-P. Ding, and X.-M. Xia. 2001. J. Gen. Physiol. 117:583-605, this issue), we have shown that some of the apparent beta3b-mediated shift in activation at low Ca(2)+ arises from rapid unblocking of inactivated channels, unlike the actions of the beta1 and beta2 subunits. Here, we compare effects of the beta3b subunit that arise from inactivation, per se, versus those that may arise from other functional effects of the subunit. In particular, we examine gating properties of the beta3b subunit and compare it to beta3b constructs lacking either the NH(2)- or COOH terminus or both. The results demonstrate that, although the NH(2) terminus appears to be the primary determinant of the beta3b-mediated shift in V(0.5) at low Ca(2)+, removal of the NH(2) terminus reveals two other interesting aspects of the action of the beta3b subunit. First, the conductance-voltage curves for activation of channels containing the beta3b subunit are best described by a double Boltzmann shape, which is proposed to arise from two independent voltage-dependent activation steps. Second, the presence of the beta3b subunit results in channels that exhibit an anomalous instantaneous outward current rectification that is correlated with a voltage dependence in the time-averaged single-channel current. The two effects appear to be unrelated, but indicative of the variety of ways that interactions between beta and alpha subunits can affect BK channel function. The COOH terminus of the beta3b subunit produces no discernible functional effects.
BK 型钾通道家族的β1 和β2 辅助亚基均能深刻调节 BK 型钙激活钾通道的表观钙敏感性。在给定的钙浓度下,尤其是钙浓度高于 1 μM 时,二者都会使半数激活电压(V(0.5))显著左移。相比之下,快速失活的β3b 辅助亚基在钙浓度低于 1 μM 时会使激活曲线左移。在同期发表的论文(Lingle, C.J., X.-H. Zeng, J.-P. Ding, and X.-M. Xia. 2001. J. Gen. Physiol. 117:583 - 605, 本期)中,我们已经表明,与β1 和β2 亚基的作用不同,低钙条件下一些表观上由β3b 介导的激活曲线左移源于失活通道的快速解除阻断。在此,我们比较了β3b 亚基本身因失活产生的效应与可能由该亚基其他功能效应产生的效应。特别地,我们研究了β3b 亚基的门控特性,并将其与缺失 NH(2)-或 COOH 末端或二者皆缺失的β3b 构建体进行比较。结果表明,尽管 NH(2)末端似乎是低钙条件下β3b 介导的 V(0.5)左移的主要决定因素,但去除 NH(2)末端揭示了β3b 亚基作用的另外两个有趣方面。首先,含有β3b 亚基的通道激活的电导 - 电压曲线最好用双玻尔兹曼形状来描述,这被认为源于两个独立的电压依赖性激活步骤。其次,β3b 亚基的存在导致通道表现出异常的瞬时外向电流整流,这与时间平均单通道电流中的电压依赖性相关。这两种效应似乎没有关联,但表明了β亚基和α亚基之间相互作用影响 BK 通道功能的多种方式。β3b 亚基的 COOH 末端未产生可辨别的功能效应。
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