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

1. Subthreshold-operating transient (A-type) K(+) currents (I(SA)s) 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(SA)s(.) 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.