BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells
BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells
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DOI：
10.1523/jneurosci.3778-14.2015
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发表时间：
2015-05-06
影响因子：
5.3
通讯作者：
Misonou, Hiroaki
中科院分区：
文献类型：
--
作者：
Hirono, Moritoshi;Ogawa, Yasuhiro;Misonou, Hiroaki
在有髓鞘的轴突中，K+通道聚集在不同的膜结构域中以调节动作电位（AP）。在Ranvier节点，Kv 7通道与Na+通道一起表达，而Kv 1通道位于Anastaparanodes节点的侧翼。钾离子通道对轴突AP的调节在快速发放投射神经元（如小脑浦肯野细胞）中尤为重要。在这里，我们发现，BK/Slo 1通道聚集在大鼠和小鼠的有髓浦肯野细胞轴突的结旁连接处。结旁连接由一组细胞粘附分子（包括Caspr）形成，位于结和结旁连接之间，将结膜区域与结间膜区域分开。值得注意的是，只有浦肯野细胞轴突具有可检测的结旁BK通道，其聚集需要通过Caspr形成结旁连接。因此，BK通道占据了浦肯野细胞轴突中的这个独特的结构域，沿着与其他K+通道复合物在节点和突触。为了研究新型结旁BK通道的生理作用，我们研究了BK通道阻滞剂对逆向AP传导的影响。我们发现，局部应用阻滞剂的轴突导致在频率高于100赫兹的逆向AP失败显着增加。我们还发现，Ni 2+引起AP上的类似的效果，表明Ni 2+敏感的Ca 2+通道的参与。此外，轴突应用BK通道阻滞剂降低了小脑深核的抑制性突触反应。因此，结旁BK通道独特地支持有髓鞘浦肯野细胞轴突中AP的高保真发射，从而支持小脑皮质的输出。
In myelinated axons, K+ channels are clustered in distinct membrane domains to regulate action potentials (APs). At nodes of Ranvier, Kv7 channels are expressed with Na+ channels, whereas Kv1 channels flank nodes at juxtaparanodes. Regulation of axonal APs by K+ channels would be particularly important in fast-spiking projection neurons such as cerebellar Purkinje cells. Here, we show that BK/Slo1 channels are clustered at the paranodal junctions of myelinated Purkinje cell axons of rat and mouse. The paranodal junction is formed by a set of cell-adhesion molecules, including Caspr, between the node and juxtaparanodes in which it separates nodal from internodal membrane domains. Remarkably, only Purkinje cell axons have detectable paranodal BK channels, whose clustering requires the formation of the paranodal junction via Caspr. Thus, BK channels occupy this unique domain in Purkinje cell axons along with the other K+ channel complexes at nodes and juxtaparanodes. To investigate the physiological role of novel paranodal BK channels, we examined the effect of BK channel blockers on antidromic AP conduction. We found that local application of blockers to the axon resulted in a significant increase in antidromic AP failure at frequencies above 100 Hz. We also found that Ni2+ elicited a similar effect on APs, indicating the involvement of Ni2+-sensitive Ca2+ channels. Furthermore, axonal application of BK channel blockers decreased the inhibitory synaptic response in the deep cerebellar nuclei. Thus, paranodal BK channels uniquely support high-fidelity firing of APs in myelinated Purkinje cell axons, thereby underpinning the output of the cerebellar cortex.