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Evidence for the presence of a novel Kv4-mediated A-type K⁺ channel-modifying factor

Marcela S. Nadal, Yimy Amarillo, Eleazar Vega-Saenz de Miera and Bernardo Rudy

1. Subthreshold-operating transient (A-type) K⁺ currents (I_SAs) are important in regulating neuronal firing frequency and in the modulation of incoming signals in dendrites. It is now known that Kv4 proteins are the principal, or pore-forming, subunits of the channels mediating I_SAs_. In addition, accessory subunits of Kv4 channels have also been identified. These either have no effect or slow down the inactivation kinetics of Kv4 channels. However, in many neuronal populations the I_SA is faster, not slower, than the current generated by channels containing only Kv4 proteins.
2. Evidence is presented for the presence in rat cerebellar mRNA of transcripts encoding a molecular factor, termed KAF, that accelerates the kinetics of Kv4 channels. Size-fractionation of cerebellar mRNA in sucrose gradients separated the high molecular weight mRNAs (4-7 kb) encoding KAF from the low molecular weight ones (1.5-3 kb) encoding factors that slow down the inactivation kinetics of Kv4 channels. The latter were identified as KChIPs using anti-KChIP antisense oligonucleotides.
3. Both anti-KChIP and anti-Kv4 antisense oligonucleotides failed to eliminate KAF's activity from the high molecular weight mRNA fraction, thus suggesting that KAF might be a novel subunit(s) that can contribute to generating native I_SA channel diversity.
4. The time course of the currents expressed by KAF-modified Kv4 channels resembles more closely the time course of the native I_SA in cerebellar granule cells.

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