CONTRASTING SUBCELLULAR-LOCALIZATION OF THE KV1.2 K-BRAIN( CHANNEL SUBUNIT IN DIFFERENT NEURONS OF RAT)

In the nervous system, a wide diversity of K+ channels are formed by t he oligomeric assembly of subunits encoded by a large number of K+ cha nnel genes. The physiological functions of a specific K+ channel subun it in vivo will be dictated in part by its subcellular location within neurons. We have used a combined in situ hybridization and immunocyto chemical approach to determine the subcellular distribution of Kv1.2, a member of the Shaker subfamily of K+ channel genes. In contrast to o ther characterized K+ channel subunits, Kv1.2 protein shows a complex differential subcellular distribution in neurons of rat brain. In some of these neurons (e.g., hippocampal and cortical pyramidal cells, and Purkinje cells), Kv1.2 is concentrated in dendrites, while in others (e.g., cerebellar basket cells), Kv1.2 is predominantly, if not exclus ively, localized to nerve terminals. Furthermore, Kv1.2 immunoreactivi ty was also detected in certain axon tracts. We hypothesize that the d ifferential sorting of Kv1.2 could result from association of Kv1.2 wi th varying heterologous K+ channel subunits in different cell types, w ith the implication that Kv 1.2 may participate in distinct heteromult imeric K+ channels in different subcellular domains. The findings sugg est that Kv1.2-containing K+ channels may play diverse functional role s in several neuronal compartments, regulating presynaptic or postsyna ptic membrane excitability, depending on the neuronal cell type.