Novel Subcellular Distribution Pattern of A-Type K+ Channels on Neuronal Surface

Potassium channels comprise the most diverse family of ion channels. In nerve cells, their critical roles in synaptic integration and output generation have been demonstrated. Here, we provide evidence for a distribution that predicts a novel role of K+ channels in the CNS. Our experiments revealed a highly selective clustering of the Kv4.3 A-type K+ channel subunits at specialized junctions between climbing fibers and cerebellar GABAergic interneurons. High-resolution ultrastructural and immunohistochemical experiments demonstrated that these junctions are distinct from known chemical and electrical (gap junctions) synapses and also from puncta adherentia. Each cerebellar interneuron contains many such K+ channel-rich specializations, which seem to be distributed throughout the somatodendritic surface. We also show that such K+ channel-rich specializations are not only present in the cerebellum but are widespread in the rat CNS. For example, mitral cells of the main olfactory bulb establish Kv4.2 subunit-positive specializations with each other. At these specializations, both apposing membranes have a high density of K+ channels, indicating bidirectional signaling. Similar specializations with pronounced coclustering of the Kv4.2 and 4.3 subunits were observed between nerve cells in the medial nucleus of the habenula. Based on our results and on the known properties of A-type K+ channels, we propose that strategically clustered K+ channels at unique membrane specializations could mediate a novel type of communication between nerve cells.