PubMed 15452711

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KChip2a , Kv1.4 , Kv3.1 , Kv4.2 , Slo1

Title: The Kv4.2 N-terminal restores fast inactivation and confers KChlP2 modulatory effects on N-terminal-deleted Kv1.4 channels.

Authors: Marc Pourrier, Daniel Herrera, Ricardo Caballero, Gernot Schram, Zhiguo Wang, Stanley Nattel

Journal, date & volume: Pflugers Arch., 2004 Dec , 449, 235-47

PubMed link:

The N-terminal end of the subunits of the voltage-gated K+ channel Kv1.4 is essential for their rapid N-type inactivation, but removal of the entire Kv4.2 N-terminus slows inactivation only moderately. In this study, we investigated the effect of substituting the Kv4.2 N-terminal for that of Kv1.4 subunits. Despite the minor role of the Kv4.2 N-terminal in Kv4.2 inactivation and the limited degree of amino acid identity between Kv1.4 and Kv4.2 N-terminals, attachment of the Kv4.2 N-terminal to inactivation-deficient, N-terminal-deleted Kv1.4 subunits restored rapid inactivation. The Kv4.2 N-terminal/N-deleted Kv1.4 chimeric construct had inactivation kinetics like those of Kv4.2, inactivation voltage-dependence resembling Kv1.4 and recovery from inactivation substantially faster than wild-type Kv1.4. Acceleration of reactivation appeared to be due to the ability of chimeric channels to recover from inactivation without passing through the open state. Co-expression of wild-type Kv1.4 with the K+ channel interacting protein-2 (KChIP2) did not alter Kvl.4 properties, but co-expression of KChIP2 with Kv4.2 N-terminal/N-deleted Kv1.4 chimeric subunits significantly increased current expression and slowed inactivation without altering the rate of recovery from inactivation. We conclude that substitution of the Kv4.2 N-terminal for that of Kv1.4 transfers a variety of properties of Kv4.2, including inactivation time-dependence, accelerated recovery from inactivation and interaction with KChIP2, to Kv1.4, indicating the ability of Kvl.4 subunits to display these properties and the sufficiency of the Kv4.2 N-terminal to convey them.