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BK and Kv3.1 Potassium Channels Control Different Aspects of Deep Cerebellar Nuclear Neurons Action Potentials and Spiking Activity

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Abstract

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.

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Acknowledgments

I want to specially thank Matthias Sausbier and Peter Ruth for a committed earlier collaboration to this project, which unfortunately led to inconclusive results due to technical problems inherent to the mouse model. Reports on this earlier collaboration have been presented in abstract form (Soc for neurosciences, 2005, 2007). I am grateful to Ute Grosshennig and Ursula Pascht for technical assistance, and for useful comments and suggestions of anonymous reviewers and the editors of this issue. Finally I want to thank Cornelius Schwarz for his comments on this manuscript.

Conflict of Interests

There is no conflict of interests related to the present study to be disclosed.

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  1. Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, Systems Neurophysiology, CIN, University of Tübingen, Otfried MüllerStr 27, 72076, Tübingen, Germany

    Christine M. Pedroarena

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Correspondence to Christine M. Pedroarena.

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Pedroarena, C.M. BK and Kv3.1 Potassium Channels Control Different Aspects of Deep Cerebellar Nuclear Neurons Action Potentials and Spiking Activity. Cerebellum 10, 647–658 (2011). https://doi.org/10.1007/s12311-011-0279-9

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