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First published online on November 21, 2001.
 Copyright © 2001 by The Physiological Society
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Received September 22, 2001
Accepted after revision November 6, 2001

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

Marcela S. Nadal1, Yimy Amarillo1, Eleazar Vega-Saenz de Miera1, and Bernardo Rudy1*

1 Department of Physiology and Neuroscience, and Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA

* To whom correspondence should be addressed. E-mail: rudyb01{at}med.nyu.edu.

1. Subthreshold-operating transient (A-type) K+ currents (ISAs) 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 ISAs. 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 ISA 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 ISA channel diversity.

4. The time course of the currents expressed by KAF-modified Kv4 channels resembles more closely the time course of the native ISA in cerebellar granule cells.




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