Dendritic Kv3.3 Potassium Channels in Cerebellar Purkinje Cells Regulate Generation and Spatial Dynamics of Dendritic Ca2+ Spikes

Zagha E, Manita S, Ross WN, Rudy B. Dendritic Kv3.3 potassium channels in cerebellar Purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes. J Neurophysiol 103: 3516-3525, 2010. First published March 31, 2010; doi:10.1152/jn.00982.2009. Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca2+ spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca2+ spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca2+](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca2+ signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca2+ influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.