Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BKbeta1-subunit leads to progressive hearing loss.
Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BKbeta1-subunit leads to progressive hearing loss.
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发表时间：
2004
影响因子：
11.1
通讯作者：
L. Rüttiger;Matthias Sausbier;U. Zimmermann;Harald Winter;Claudia Braig;J. Engel;Martina Knirsch;C. Arntz;Patricia Langer;B. Hirt;Marcus Müller;I. Köpschall;M. Pfister;S. Münkner;K. Rohbock;I. Pfaff;A. Rüsch;P. Ruth;M. Knipper
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文献类型：
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作者：
L. Rüttiger;Matthias Sausbier;U. Zimmermann;Harald Winter;Claudia Braig;J. Engel;Martina Knirsch;C. Arntz;Patricia Langer;B. Hirt;Marcus Müller;I. Köpschall;M. Pfister;S. Münkner;K. Rohbock;I. Pfaff;A. Rüsch;P. Ruth;M. Knipper
大电导电压和钙激活钾(BK)通道在耳蜗内毛细胞的信号转导过程中起重要作用。BK通道已被证明是由成孔的α亚基和辅助的β1亚基共同表达的。通过对BK通道α(BKalpha-/-)和β1-亚基(BKbeta1-/-)基因敲除小鼠的听力和耳蜗表型的分析，我们证明BKbeta1-/-小鼠的听力功能和耳蜗结构正常。同样，在出生后的前4周，BKalpha/-小鼠最令人惊讶的是没有表现出任何明显的听力障碍。BKalpha-/-小鼠出生后大约8周才出现高频听力损失，并伴有失真产物耳声发射的缺失，表明外毛细胞(OHC)功能障碍。听力损失与耳蜗基底部和中回毛细胞膜上KCNQ4钾通道的丧失有关，先于毛细胞退化，并导致与药物阻断KCNQ4通道所引起的相似的表型。尽管BK基因缺失、OHC细胞中KCNQ4缺失和OHC变性之间的实际联系还需要进一步研究，但数据已经表明，人类编码BK的SLO1基因突变是进行性耳聋的易感因素，类似于KCNQ4钾通道突变。
The large conductance voltage- and Ca2+-activated potassium (BK) channel has been suggested to play an important role in the signal transduction process of cochlear inner hair cells. BK channels have been shown to be composed of the pore-forming alpha-subunit coexpressed with the auxiliary beta1-subunit. Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha-/-) and beta1-subunit (BKbeta1-/-) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta1-/- mice. During the first 4 postnatal weeks also, BKalpha-/- mice most surprisingly did not show any obvious hearing deficits. High-frequency hearing loss developed in BKalpha-/- mice only from approximately 8 weeks postnatally onward and was accompanied by a lack of distortion product otoacoustic emissions, suggesting outer hair cell (OHC) dysfunction. Hearing loss was linked to a loss of the KCNQ4 potassium channel in membranes of OHCs in the basal and midbasal cochlear turn, preceding hair cell degeneration and leading to a similar phenotype as elicited by pharmacologic blockade of KCNQ4 channels. Although the actual link between BK gene deletion, loss of KCNQ4 in OHCs, and OHC degeneration requires further investigation, data already suggest human BK-coding slo1 gene mutation as a susceptibility factor for progressive deafness, similar to KCNQ4 potassium channel mutations.