Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvβ1.1 A-type K
            <sup>+</sup>
            channels

Jow, Flora; Zhang, Zhihao; Kopsco, David C.; Carroll, Karen C.; Wang, Kewei

doi:10.1073/pnas.0402081101

Cited by 26 publications

(26 citation statements)

References 33 publications

(31 reference statements)

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“…In the control experiments, with application of 10 μM BAPTA-AM, the inactivation of Kv1.4 channel was not altered, indicating that the inactivation of Kv1.4 channel itself is Ca 2+ -independent, which is in agreement with the conclusion of Jow et al [41]. However, when Kv1.4 was coexpressed with synaptotagmin I, the inactivation of Kv1.4 channel was slowed and this change was affected by Ca 2+ in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 90%

“…It has been reported that Kvβ1.1 can further potentiate the fast inactivation of Kv1.4 channel [39,40]. Jow et al [41] also found a faster inactivation of Kv1.4 current when Kv1.4 and Kvβ1.1 were coexpressed in oocytes. Kvβ1.2 has been shown to increase the rate of inactivation of Kv1.4 and slow the rate of recovery from inactivation, and the mutation experiments indicated that Kvβ1.2C-terminus (Kvβ1.2-C) is responsible for interaction with the channel [42].…”

Section: Discussionmentioning

confidence: 99%

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Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus

Xie

Guo

et al. 2014

Mol Brain

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BackgroundThe voltage-gated potassium channel Kv1.4 is an important A-type potassium channel and modulates the excitability of neurons in central nervous system. Analysis of the interaction between Kv1.4 and its interacting proteins is helpful to elucidate the function and mechanism of the channel.ResultsIn the present research, synaptotagmin I was for the first time demonstrated to be an interacting protein of Kv1.4 and its interaction with Kv1.4 channel did not require the mediation of other synaptic proteins. Using patch-clamp technique, synaptotagmin I was found to delay the inactivation of Kv1.4 in HEK293T cells in a Ca2+-dependent manner, and this interaction was proven to have specificity. Mutagenesis experiments indicated that synaptotagmin I interacted with the N-terminus of Kv1.4 and thus delayed its N-type fast inactivation.ConclusionThese data suggest that synaptotagmin I is an interacting protein of Kv1.4 channel and, as a negative modulator, may play an important role in regulating neuronal excitability and synaptic efficacy.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus

Xie

Guo

et al. 2014

Mol Brain

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“…For electrophysiology, WT or mutant cDNA constructs of either Kv4.3 or KChIPs were subcloned into pBluescript KSM (8). cRNAs were transcribed in vitro using the T3 mMESSAGE Machine kit (Ambion) following linearization of the cDNA construct with NotI enzyme.…”

Section: Methodsmentioning

confidence: 99%

Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation

Liang

Wang

Hao

et al. 2009

Journal of Biological Chemistry

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Dynamic inactivation in Kv4 A-type K؉ current plays a critical role in regulating neuronal excitability by shaping action potential waveform and duration. Multifunctional auxiliary KChIP1-4 subunits, which share a high homology in their C-terminal core regions, exhibit distinctive modulation of inactivation and surface expression of pore-forming Kv4 subunits. However, the structural differences that underlie the functional diversity of Kv channel-interacting proteins (KChIPs) remain undetermined. Here we have described the crystal structure of KChIP4a at 3.0 Å resolution, which shows distinct N-terminal ␣-helices that differentiate it from other KChIPs. Biochemical experiments showed that competitive binding of the Kv4.3 N-terminal peptide to the hydrophobic groove of the core of KChIP4a causes the release of the KChIP4a N terminus that suppresses the inactivation of Kv4.3 channels. Electrophysiology experiments confirmed that the first N-terminal ␣-helix peptide (residues 1-34) of KChIP4a, either by itself or fused to N-terminal truncated Kv4.3, can confer slow inactivation. We propose that N-terminal binding of Kv4.3 to the core of KChIP4a mobilizes the KChIP4a N terminus, which serves as the slow inactivation gate.A-type inactivation, a rapid process of channel closing, leads to the reduction or elimination of potassium currents that can be dynamically regulated by a variety of intracellular factors. These include neurotransmitters, kinases, second messengers, and ␤-subunits, resulting in diverse mechanisms for the control of potassium channel activity (1-9).

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“…All WT or Kv4.3 mutants were constructed and inserted into pEGFP-N1 vectors (Clontech Laboratories, Mountain View, CA) with double restriction sites of HindIII and PstI. For cDNA constructs used for electrophysiological studies, they were made in pBluescript KSM oocyte vectors with restriction sites of SalI and EcoRI [15]. All restriction enzymes were purchased from either New England Biolabs, Inc or Takara.…”

Section: Molecular Biologymentioning

confidence: 99%

“…For oocyte expression, WT or mutant cDNA constructs of either Kv4.3 or KChIP1 were subcloned into pBluescript KSM [15]. cRNAs were in vitro transcribed using the T3 mMESSAGE Machine kit (Ambion) following linearization of cDNA construct with NotI enzyme.…”

Section: Electrophysiological Recordings In Xenopus Oocytesmentioning

confidence: 99%

Enhanced Trafficking of Tetrameric Kv4.3 Channels by KChIP1 Clamping

2008

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The cytoplamsic auxiliary KChIPs modulate surface expression and gating properties of Kv4 channels. Recent co-crystal structure of Kv4.3 N-terminus and KChIP1 reveals a clamping action of the complex in which a single KChIP1 molecule laterally binds two neighboring Kv4.3 N-termini at different locations, thus forming two contact interfaces involved in the protein-protein interaction. In the second interface, it functions to stabilize the tetrameric assembly, but the role it plays in channel trafficking remains elusive. In this study, we examined the effects of KChIP1 on Kv4 protein trafficking in COS-7 cells expressing EGFP-tagged Kv4.3 channels using confocal microscopy. Mutations either in KChIP1 (KChIP1 L39E-Y57A-K61A) or Kv4.3 (Kv4.3 E70A-F73E) that disrupt the protein-protein interaction within the second interface can reduce surface expression of Kv4 channel proteins. Kv4.3 C110A, the Zn2+ binding site mutation in T1 domain, that disrupts the tetrameric assembly of the channels can be rescued by WT KChIP1, but not the KChIP1 triple mutant. These results were further confirmed by whole cell current recordings in oocytes. Our findings show that key residues of second interface involved in stabilizing tetrameric assembly can regulate the channel trafficking, indicating an intrinsic link between tetrameric assembly and channel trafficking. The results also suggest that formation of octameric Kv4 and KChIP complex by KChIPs clamping takes place before their trafficking to final destination on the cell surface.

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Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvβ1.1 A-type K ⁺ channels

Cited by 26 publications

References 33 publications

Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus

Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus

Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation

Enhanced Trafficking of Tetrameric Kv4.3 Channels by KChIP1 Clamping

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Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvβ1.1 A-type K + channels

Cited by 26 publications

References 33 publications

Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus

Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus

Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation

Enhanced Trafficking of Tetrameric Kv4.3 Channels by KChIP1 Clamping

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Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvβ1.1 A-type K ⁺ channels