Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, United Kingdom, and Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
J Neurosci. 2014 Apr 16;34(16):5505-14. doi: 10.1523/JNEUROSCI.4086-13.2014.
Tip links between adjacent stereocilia are believed to gate mechano-electrical transducer (MET) channels and mediate the electrical responses of sensory hair cells. We found that mouse auditory hair cells that lack tip links due to genetic mutations or exposure to the Ca(2+) chelator BAPTA can, however, still respond to mechanical stimuli. These MET currents have unusual properties and are predominantly of the opposite polarity relative to those measured when tip links are present. There are other striking differences, for example, the channels are usually all closed when the hair cell is not stimulated and the currents in response to strong stimuli can be substantially larger than normal. These anomalous MET currents can also be elicited early in development, before the onset of mechano-electrical transduction with normal response polarity. Current-voltage curves of the anomalous MET currents are linear and do not show the rectification characteristic of normal MET currents. The permeant MET channel blocker dihydrostreptomycin is two orders of magnitude less effective in blocking the anomalous MET currents. The findings suggest the presence of a large population of MET channels with pore properties that are distinct from those of normal MET channels. These channels are not gated by hair-bundle links and can be activated under a variety of conditions in which normal tip-link-mediated transduction is not operational.
相邻静纤毛之间的连接点被认为是机械电换能器(MET)通道的门控,介导感觉毛细胞的电反应。我们发现,由于基因突变或暴露于 Ca(2+)螯合剂 BAPTA,缺乏连接点的小鼠听觉毛细胞仍然可以对机械刺激做出反应。这些 MET 电流具有异常的特性,与存在连接点时测量到的电流相比,主要是相反的极性。还有其他显著的差异,例如,当毛细胞未受到刺激时,通道通常全部关闭,而对强刺激的响应电流可能比正常情况下大得多。这些异常的 MET 电流也可以在机械电转导出现正常反应极性之前的早期发育阶段被诱发。异常 MET 电流的电流-电压曲线是线性的,不显示正常 MET 电流的整流特性。通透性 MET 通道阻断剂二氢链霉素在阻断异常 MET 电流方面的效果要低两个数量级。这些发现表明存在大量具有与正常 MET 通道不同的孔特性的 MET 通道。这些通道不受毛束连接点的门控,并且可以在多种情况下被激活,而正常的连接点介导的转导在这些情况下无法正常运作。