Expression of BK-type calcium-activated potassium channel splice variants during chick cochlear development.
Expression of BK-type calcium-activated potassium channel splice variants during chick cochlear development.
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DOI：
10.1002/cne.22352
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Duncan RK
中科院分区：
文献类型：
--
作者：
Kim JM;Beyer R;Morales M;Chen S;Liu LQ;Duncan RK
大电导钙激活钾（BK）电流的出现是听毛细胞功能成熟的标志。这种快速激活电流的获得使所有脊椎动物的高频分级受体电位和非哺乳动物的电调谐机制成为可能。编码BK α亚基的基因是高度选择性剪接的，由此产生的通道亚型的变化可能有助于听力开始时的功能多样性。我们检测了9个BK α替代外显子的组织特异性，并使用定量聚合酶链反应（qPCR）研究了鸡耳蜗发育过程中表达的变化。每个替代广泛表达在几个组织中，除了插入附近的C-末端Ca 2+传感域，这似乎是脑特异性的。在通道的膜结合核心中的唯一替代形式在脑和肌肉中表达，但在耳蜗中未检测到。其余的变体中，有三个在听力和BK电流采集开始前表达增加。这三种变体导致Ca 2+敏感性降低或细胞内滞留增加，这些特征不容易解释胚胎第18-19天钙敏感电流的出现。其他变体的表达水平在E15时成熟且稳定，即获得电流前几天。采用膜片钳电生理学和免疫细胞化学方法检测C-末端亚型的表面表达。表现出稳健的表面表达的C-末端变体在E18时出现在膜中，即使转录本在从E12开始的发育过程中没有变化。这些结果表明，延迟蛋白质合成和运输/支架通道亚基的基础上的后期收购的BK电流在耳蜗毛细胞。
The appearance of large-conductance, calcium-activated potassium (BK) current is a hallmark of functional maturation in auditory hair cells. Acquisition of this fast-activating current enables high-frequency, graded receptor potentials in all vertebrates and an electrical tuning mechanism in nonmammals. The gene encoding BK α subunits is highly alternatively spliced, and the resulting variations in channel isoforms may contribute to functional diversity at the onset of hearing. We examined the tissue specificity of nine BK α alternative exons and investigated changes in expression during chick cochlear development using quantitative polymerase chain reaction (qPCR). Each alternative was widely expressed in several tissues except for an insert near the C-terminus Ca2+ sensing domain, which appeared brain-specific. The only alternative form in the membrane-bound core of the channel was expressed in brain and muscle but was undetected in cochlea. Of the remaining variants, three increased in expression prior to the onset of hearing and acquisition of BK currents. These three variants cause decreased Ca2+ sensitivity or increased intracellular retention, traits that would not easily explain the advent of calcium-sensitive currents at embryonic day (E)18–19. Expression levels of other variants were mature and stable by E15, days before currents were acquired. Surface expression of C-terminal isoforms was examined using patch-clamp electrophysiology and immunocytochemistry. C-terminal variants that exhibit robust surface expression appeared in the membrane at E18, even though transcripts were unchanged during development starting from E12. These results indicate that delays in protein synthesis and trafficking/scaffolding of channel subunits underlie the late acquisition of BK currents in cochlear hair cells.
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DOI：
10.1085/jgp.105.1.49
发表时间：
1995-01
期刊：
The Journal of general physiology
影响因子：
--
作者：
Art JJ;Wu YC;Fettiplace R
通讯作者：
Fettiplace R
影响因子：
3.5
作者：
Beisel, Kirk W.;Rocha-Sanchez, Sonia M.;Davis, Robin L.
通讯作者：
Davis, Robin L.
DOI：
10.1152/ajpheart.00789.2006
发表时间：
2007-07-01
影响因子：
4.8
作者：
Kang, Sung Hyun;Park, Won Sun;Han, Jin
通讯作者：
Han, Jin
影响因子：
3.3
作者：
Kim, E. Y.;Ridgway, L. D.;Dryer, S. E.
通讯作者：
Dryer, S. E.
影响因子：
5.5
作者：
Lu, R;Alioua, A;Toro, L
通讯作者：
Toro, L