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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 583/3/959    most recent jphysiol.2007.139550v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Van Hoorick, D. Articles by Snyders, D. J. Search for Related Content PubMed PubMed Citation Articles by Van Hoorick, D. Articles by Snyders, D. J. Related Collections Neuroscience

¹ Laboratory for Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium

The KChIP1b splice variant has been shown to induce slow recovery from inactivation for Kv4.2 whereas KChIP1a enhanced the recovery. Both splice variants differ only by the insertion of the exon1b, rich in aromatic residues (5/11). We analysed in detail the modifications of Kv4.2 gating induced by the KChIP1b splice variant and the role for the aromatic cluster in KChIP1b in inducing these changes. By substituting alanine for the aromatic residues individually or in combination, we could convert the KChIP1b recovery behaviour into that of KChIP1a. The replacement of one or two aromatic residues resulted in a partial restitution of the KChIP1a recovery behaviour. When three aromatic residues were replaced in the exon1b, the recovery from inactivation was fast with time constants that were similar to those obtained with KChIP1a. Moreover, similar findings were observed for closed state inactivation and for the voltage dependence of inactivation. Thus, reduction of the side chain bulkiness in exon1b resulted in the conversion of the KChIP1b phenotype into the KChIP1a phenotype. These results indicate that the aromatic cluster in exon1b modulates the transitions towards and from the closed inactivated states and the steady state distribution over the respective states.

(Received 26 June 2007; accepted after revision 17 July 2007; first published online 26 July 2007)
Corresponding author D. J. Snyders: Laboratory for Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. Email: dirk.snyders{at}ua.ac.be