DIFFERENTIAL EXPRESSION OF KV4 K-TYPE) CURRENTS IN RAT-BRAIN( CHANNELSUBUNITS MEDIATING SUBTHRESHOLD TRANSIENT K+ (A)

The mammalian Kv4 gene subfamily and its Drosophila Shal counterpart e ncode proteins that form fast inactivating K+ channels that activate a nd inactivate at subthreshold potentials and recover from inactivation at a faster rate than other inactivating Kv channels. Taken together, the properties of Kv4 channels compare best with those of low-voltage activating ''A-currents'' present in the neuronal somatodendritic com partment and widely reported across several types of central and perip heral neurons, as well as the (Ca2+-independent) transient outward pot assium conductance of heart cells (I-to). Three distinct genes have be en identified that encode mammalian Shal homologs (Kv4.1, Kv4.2, and K v4.3), of which the latter two are abundant in rat adult brain and hea rt tissues. The distribution in the adult rat brain of the mRNA transc ripts encoding the three known Kv4 subunits was studied by in situ hyb ridization histochemistry. Kv4.1 signals are very faint, suggesting th at Kv4.1 mRNAs are expressed at very low levels, but Kv4.2 and Kv4.3 t ranscripts appear to be abundant and each produces a unique pattern of expression. Although there is overlap expression of Kv4.2 and Kv4.3 t ranscripts in several neuronal populations, the dominant feature is on e of differential, and sometimes reciprocal expression. For example, K v4.2 transcripts are the predominant form in the caudate-putamen, pont ine nucleus and several nuclei in the medula, whereas the substantia n igra pars compacta, the restrosplenial cortex, the superior colliculus , the raphe, and the amygdala express mainly Kv4.3. Some brain structu res contain both Kv4.2 and Kv4.3 mRNAs but each dominates in distinct neuronal subpopulations. For example, in the olfactory bulb Kv4.2 domi nates in granule cells and Kv4.3 in periglomerular cells. In the hippo campus Kv4.2 is the most abundant isoform in CA1 pyramidal cells, wher eas only Kv4.3 is expressed in interneurons. Both are abundant in CA2- CA3 pyramidal cells and in granule cells of the dentate gyrus, which a lso express Kv4.1. In the dorsal thalamus strong Kv4.3 signals are see n in several lateral nuclei, whereas medial nuclei express Kv4.2 and K v4.3 at moderate to low levels. In the cerebellum Kv4.3, but not Kv4.2 , is expressed in Purkinje cells and molecular layer interneurons. In the cerebellar granule cell layer, the reciprocity between Kv4.2 and K v4.3 is observed in subregions of the same neuronal population. In fac t, the distribution of Kv4 channel transcripts in the cerebellum defin es a new pattern of compartmentation of the cerebellar cortex and the first one involving molecules directly involved in signal processing.