Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, Systems Neurophysiology, CIN, University of Tübingen, Otfried Müller Strasse 27, Tübingen, Germany.
Cerebellum. 2011 Dec;10(4):647-58. doi: 10.1007/s12311-011-0279-9.
Deep cerebellar nuclear neurons (DCNs) display characteristic electrical properties, including spontaneous spiking and the ability to discharge narrow spikes at high frequency. These properties are thought to be relevant to processing inhibitory Purkinje cell input and transferring well-timed signals to cerebellar targets. Yet, the underlying ionic mechanisms are not completely understood. BK and Kv3.1 potassium channels subserve similar functions in spike repolarization and fast firing in many neurons and are both highly expressed in DCNs. Here, their role in the abovementioned spiking characteristics was addressed using whole-cell recordings of large and small putative-glutamatergic DCNs. Selective BK channel block depolarized DCNs of both groups and increased spontaneous firing rate but scarcely affected evoked activity. After adjusting the membrane potential to control levels, the spike waveforms under BK channel block were indistinguishable from control ones, indicating no significant BK channel involvement in spike repolarization. The increased firing rate suggests that lack of DCN-BK channels may have contributed to the ataxic phenotype previously found in BK channel-deficient mice. On the other hand, block of Kv3.1 channels with low doses of 4-aminopyridine (20 μM) hindered spike repolarization and severely depressed evoked fast firing. Therefore, I propose that despite similar characteristics of BK and Kv3.1 channels, they play different roles in DCNs: BK channels control almost exclusively spontaneous firing rate, whereas DCN-Kv3.1 channels dominate the spike repolarization and enable fast firing. Interestingly, after Kv3.1 channel block, BK channels gained a role in spike repolarization, demonstrating how the different function of each of the two channels is determined in part by their co-expression and interplay.
小脑深部核神经元（DCNs）表现出特征性的电生理特性，包括自发性放电和高频时窄峰放电的能力。这些特性被认为与处理抑制性浦肯野细胞输入和向小脑靶区传递定时信号有关。然而，其潜在的离子机制尚不完全清楚。BK 和 Kv3.1 钾通道在许多神经元的峰电位复极化和快速放电中具有相似的功能，并且在 DCNs 中均高度表达。在这里，使用大、小假定谷氨酸能 DCN 的全细胞膜片钳记录研究了它们在上述峰电位特征中的作用。选择性 BK 通道阻断剂使两种 DCN 去极化，并增加自发性放电率，但对诱发活动影响不大。在将膜电位调整到对照水平后，BK 通道阻断下的峰电位波形与对照条件下的峰电位波形无法区分，表明 BK 通道对峰电位复极化没有显著影响。放电率的增加表明，缺乏 DCN-BK 通道可能导致以前在 BK 通道缺陷小鼠中发现的共济失调表型。另一方面，用低剂量 4-氨基吡啶（20 μM）阻断 Kv3.1 通道会阻碍峰电位复极化，并严重抑制诱发的快速放电。因此，我提出尽管 BK 和 Kv3.1 通道具有相似的特性，但它们在 DCNs 中发挥不同的作用：BK 通道几乎完全控制自发性放电率，而 DCN-Kv3.1 通道主导峰电位复极化，并使快速放电成为可能。有趣的是，在 Kv3.1 通道阻断后，BK 通道在峰电位复极化中发挥作用，表明两个通道的不同功能部分取决于它们的共表达和相互作用。
