Mossy fibre contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons

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Abstract
Compartmentalization of neuronal function is achieved by highly localized clustering of ion channels in discrete subcellular membrane domains. Voltage‐gated potassium (Kv) channels exhibit highly variable cellular and subcellular patterns of expression. Here, we describe novel activity‐dependent synaptic targeting of Kv4.2, a dendritic Kv channel, in cerebellar granule cells (GCs). In vivo, Kv4.2 channels are highly expressed in cerebellar glomeruli, specializations of GC dendrites that form synapses with mossy fibres. In contrast, in cultured GCs, Kv4.2 was found localized, not to dendrites but to cell bodies. To investigate the role of synaptic contacts, we developed a co‐culture system with cells from pontine grey nucleus, the origin of mossy fibres. In these co‐cultures, synaptic structures formed, and Kv4.2 was now targeted to these synaptic sites in a manner dependent on synaptic activity. Activation of NMDA‐ and/or AMPA‐type glutamate receptors was necessary for the targeting of Kv4.2 in co‐cultures, and activation of these receptor systems in GC monocultures induced dendritic targeting of Kv4.2 in the absence of synapse formation. These results indicate that the proper targeting of Kv4.2 channels is dynamically regulated by synaptic activity. This activity‐dependent regulation of Kv4.2 localization provides a crucial yet dynamic link between synaptic activity and dendritic excitability.