BK Channels Mediate Pathway-Specific Modulation of Visual Signals in the In Vivo Mouse Retina

BK Channels Mediate Pathway-Specific Modulation of Visual Signals in the In Vivo Mouse Retina
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DOI:
10.1523/jneurosci.4654-11.2012
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发表时间:
2012-04-04
影响因子:
5.3
通讯作者:
Schubert, Timm
Schubert, Timm
中科院分区:
医学1区
文献类型:
--
作者:
Tanimoto, Naoyuki;Sothilingam, Vithiyanjali;Schubert, Timm

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大电导Ca ~(2+)激活的K ~+(BK)通道在神经系统中的调节作用已被广泛研究。在视网膜中,已经显示BK通道在调节从A17无长突细胞到视杆双极细胞(RBC)的反馈中起关键作用。在这里,我们使用视网膜电图检查BK通道的功能作用,杆和锥视觉在视网膜中的体内使用基因工程小鼠缺乏功能BK通道(BK-/-)。在暗适应和光适应条件下,BK通道的缺乏对光感受器活性没有影响,表明这些离子通道不调节光感受器反应。在双极细胞水平上,Bk-/-小鼠中归因于RBC的ERG信号在低暗视刺激强度下与野生型小鼠中的ERG信号没有差异。然而,在高暗视觉和低中间视觉刺激强度,接近RBC饱和,反映RBC活性的ERG信号的显着减少存在于BK-/-视网膜。在较高的中间视觉刺激强度激活红细胞和锥双极细胞(CBCs),没有差异的ERG信号之间的BK-/-和野生型mice被发现。在明视刺激的范例中,ON-和OFF-CBCs在BK-/-和野生型视网膜的活动是不可区分的。这些研究结果表明,BK通道在双极细胞水平在中等刺激条件下调节体内视觉反应。
The modulatory role of large-conductance Ca2+-activated K+ (BK) channels in the nervous system has been extensively studied. In the retina, it has been shown that BK channels play a pivotal role in modulating feedback from A17 amacrine cells to rod bipolar cells (RBCs). Here, we used electroretinography to examine the functional role of BK channels for rod and cone vision in the retina in vivo using a genetically engineered mouse lacking functional BK channels (Bk-/-). Under dark-adapted and light-adapted conditions, the lack of BK channels had no effect on photoreceptor activity, suggesting that these ion channels do not modulate photoreceptor responses. At the bipolar cell level, the ERG signals attributed to RBCs in Bk-/- mice were not different from those in wild-type mice at low scotopic stimulus intensities. However, at high scotopic and low mesopic stimulus intensities, close to RBC saturation, a significant reduction of ERG signals reflecting RBC activity was present in the Bk-/- retina. At higher mesopic stimulus intensities activating both RBCs and cone bipolar cells (CBCs), no difference in ERG signals between Bk-/- and wild-type mice was found. In photopic stimulus paradigms, activity of ON- and OFF-CBCs in Bk-/- and wild-type retinae was indistinguishable. These findings demonstrate that BK channels modulate visual responses in vivo at the bipolar cell level at intermediate stimulus conditions.