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K(V)4.3 N-terminal deletion mutant ?2-39: effects on inactivation and recovery characteristics in both the absence and presence of KChIP2b.

ABSTRACT: Gating transitions in the K(V)4.3 N-terminal deletion mutant ?2-39 were characterized in the absence and presence of KChIP2b. We particularly focused on gating characteristics of macroscopic (open state) versus closed state inactivation (CSI) and recovery. In the absence of KChIP2b ?2-39 did not significantly alter the steady-state activation "a(4)" relationship or general CSI characteristics, but it did slow the kinetics of deactivation, macroscopic inactivation, and macroscopic recovery. Recovery kinetics (for both WT K(V)4.3 and ?2-39) were complicated and displayed sigmoidicity, a process which was enhanced by ?2-39. Deletion of the proximal N-terminal domain therefore appeared to specifically slow mechanisms involved in regulating gating transitions occurring after the channel open state(s) had been reached. In the presence of KChIP2b ?2-39 recovery kinetics (from both macroscopic and CSI) were accelerated, with an apparent reduction in initial sigmoidicity. Hyperpolarizing shifts in both "a(4)" and isochronal inactivation "i" were also produced. KChIP2b-mediated remodeling of K(V)4.3 gating transitions was therefore not obligatorily dependent upon an intact N-terminus. To account for these effects we propose that KChIP2 regulatory domains exist in K(V)4.3 a subunit regions outside of the proximal N-terminal. In addition to regulating macroscopic inactivation, we also propose that the K(V)4.3 N-terminus may act as a novel regulator of deactivation-recovery coupling.

SUBMITTER: Hovind LJ

PROVIDER: S-EPMC3052207 | biostudies-literature | 2011 Jan-Feb

REPOSITORIES: biostudies-literature

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K(V)4.3 N-terminal deletion mutant Δ2-39: effects on inactivation and recovery characteristics in both the absence and presence of KChIP2b.

Hovind Laura J LJ Skerritt Matthew R MR Campbell Donald L DL

Channels (Austin, Tex.) 20110101 1

Gating transitions in the K(V)4.3 N-terminal deletion mutant Δ2-39 were characterized in the absence and presence of KChIP2b. We particularly focused on gating characteristics of macroscopic (open state) versus closed state inactivation (CSI) and recovery. In the absence of KChIP2b Δ2-39 did not significantly alter the steady-state activation "a(4)" relationship or general CSI characteristics, but it did slow the kinetics of deactivation, macroscopic inactivation, and macroscopic recovery. Recov ...[more]

PMID: 21057209

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Dataset Information

K(V)4.3 N-terminal deletion mutant ?2-39: effects on inactivation and recovery characteristics in both the absence and presence of KChIP2b.

Publications

K(V)4.3 N-terminal deletion mutant Δ2-39: effects on inactivation and recovery characteristics in both the absence and presence of KChIP2b.

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