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The Journal of Neuroscience, February 6, 2008, 28(6):1291-1300; doi:10.1523/JNEUROSCI.4358-07.2008

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Cellular/Molecular
Kv3.3 Channels at the Purkinje Cell Soma Are Necessary for Generation of the Classical Complex Spike Waveform

Edward Zagha,^1,3,4 Eric J. Lang,¹ and Bernardo Rudy^1,2,3

Departments of ¹Physiology and Neuroscience and ²Biochemistry, ³Smilow Neuroscience Program, and ⁴Medical Scientist Training Program, New York University School of Medicine, New York, New York 10016

Correspondence should be addressed to Dr. Bernardo Rudy, Smilow Neuroscience Program, New York University School of Medicine, 522 First Avenue, Sixth Floor, New York, NY 10016. Email: rudyb01{at}med.nyu.edu

Voltage-gated potassium channel subunit Kv3.3 is prominently expressed in cerebellar Purkinje cells and is known to be important for cerebellar function, as human and mouse movement disorders result from mutations in Kv3.3. To understand these behavioral deficits, it is necessary to know the role of Kv3.3 channels on the physiological responses of Purkinje cells. We studied the function of Kv3.3 channels in regulating the synaptically evoked Purkinje cell complex spike, the massive postsynaptic response to the activation of climbing fiber afferents, believed to be fundamental to cerebellar physiology. Acute slice recordings revealed that Kv3.3 channels are required for generation of the repetitive spikelets of the complex spike. We found that spikelet expression is regulated by somatic, and not by dendritic, Kv3 activity, which is consistent with dual somatic–dendritic recordings that demonstrate spikelet generation at axosomatic membranes. Simulations of Purkinje cell Na⁺ currents show that the unique electrical properties of Kv3 and resurgent Na⁺ channels are coordinated to limit accumulation of Na⁺ channel inactivation and enable rapid, repetitive firing. We additionally show that Kv3.3 knock-out mice produce altered complex spikes in vitro and in vivo, which is likely a cellular substrate of the cerebellar phenotypes observed in these mice. This characterization presents new tools to study complex spike function, cerebellar signaling, and Kv3.3-dependent human and mouse phenotypes.

Key words: Kv3; potassium channels; Purkinje cell; complex spike; spinocerebellar ataxia; excitability

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Received Sept. 23, 2007; revised Dec. 17, 2007; accepted Dec. 18, 2007.

Correspondence should be addressed to Dr. Bernardo Rudy, Smilow Neuroscience Program, New York University School of Medicine, 522 First Avenue, Sixth Floor, New York, NY 10016. Email: rudyb01{at}med.nyu.edu

This article has been cited by other articles:

				J. T. Davie, B. A. Clark, and M. Hausser The Origin of the Complex Spike in Cerebellar Purkinje Cells J. Neurosci., July 23, 2008; 28(30): 7599 - 7609. [Abstract] [Full Text] [PDF]

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