Contribution of BKCa2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea
Contribution of BKCa2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea
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DOI：
10.1152/jn.01155.2002
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发表时间：
2003-07-01
影响因子：
2.5
通讯作者：
Dulon, D
中科院分区：
文献类型：
--
作者：
Skinner, LJ;Enée, V;Dulon, D
BK Ca2+激活的K+通道对豚鼠耳蜗听神经传递的贡献。[J]中国生物医学工程学报，2009,31(2):391 - 391。2003年2月12日首次出版；10.1152 / jn.01155.2002。已知大电导钙活化钾（BK）通道在低等脊椎动物的毛细胞功能中发挥重要作用，这些通道决定电调谐和神经递质释放的调节。相比之下，我们对BK通道在哺乳动物耳蜗中的作用知之甚少。在本研究中，我们在豚鼠耳蜗灌注特定毒素，以表征BK通道在耳蜗神经传递中的作用。耳蜗内灌注白蜡毒素（ChTX）或伊比蛇毒素（IbTX）可在数分钟内可逆地降低听神经的复合动作电位（CAP）。耳蜗微音（f1 = 8 kHz和f2 = 9.68 kHz）及其畸变产物（2f1-f2 DPCM）基本不受影响，表明BK特异性毒素不改变外毛细胞（ohc）的主动耳蜗放大。我们还测试了这些毒素对分离豚鼠内毛细胞（IHCs）全细胞电压依赖性膜电流的影响。ChTX和IbTX可逆地降低了快速向外电流（激活在-40 mV以上，峰值在0 mV，平均激活时间常数τ在0.5到1 ms之间）。在细胞外应用钡离子时也观察到类似的快速向外电流阻滞，我们认为钡离子通过Ca2+通道渗透并阻断BK通道。Slo反义核糖探针和免疫细胞化学原位杂交表明，BK通道在ihc和螺旋神经节中表达强烈，在OHCs中表达程度较低。总之，我们的研究结果清楚地揭示了BK通道在哺乳动物耳蜗神经传递中的重要性，并表明在突触前水平，快速BK通道是ihc复极电流的重要组成部分。
Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea. J Neurophysiol 90: 320-332, 2003. First published February 12, 2003; 10.1152/jn.01155.2002. Large-conductance calcium-activated potassium ( BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above -40 mV, peaking at 0 mV with a mean activation time constant tau ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+ channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs.