Journal of Physiology-London vol:583 issue:3 pages:959-969
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 KChIP I a phenotype. These results indicate that the aromatic clusterin exon1b modulates the transitions towards and from the closed inactivated states and the steady state distribution over the respective states.