A Fundamental Role for KChIPs in Determining the Molecular Properties and Trafficking of Kv4.2 Potassium Channels

Shibata, Riichi; Misonou, Hiroaki; Campomanes, Claire R.; Anderson, Anne E.; Schrader, Laura A.; Doliveira, Lisa C.; Carroll, Karen; Sweatt, J. David; Rhodes, Kenneth J.; Trimmer, James S.

doi:10.1074/jbc.m306142200

Cited by 234 publications

(307 citation statements)

References 59 publications

Supporting

Mentioning

283

Contrasting

Order By: Relevance

“…The co-expression of KChIP2-myc with Kv4.3-V5 resulted in a more rapid recovery from inactivation and translocation of the channel to the cell surface ( Fig. 1) as was reported for the wild type proteins (36,37). Kv4.3 is partially internalized in the absence of KChIP2 (Fig.…”

Section: Resultssupporting

confidence: 49%

“…To conduct more detailed studies of the mechanism of I to regulation by angiotensin II, we co-expressed Kv4.3 with the AT1 receptor in HEK 293 cells. Recently, it was shown that ion transport by pore-forming ␣-subunits of the Kv4.x family depends on the presence of calcium sensing proteins, KChIPs, which form complexes with them and deliver the ␣-subunits to the cell surface (36,37). For this reason we co-expressed Kv4.3 with its ␤-subunit KChIP2.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin Receptor Type 1 Forms a Complex with the Transient Outward Potassium Channel Kv4.3 and Regulates Its Gating Properties and Intracellular Localization

Doronin

Potapova

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

We report a novel signal transduction complex of the angiotensin receptor type 1. In this complex the angiotensin receptor type 1 associates with the potassium channel ␣-subunit Kv4.3 and regulates its intracellular distribution and gating properties. Electrophysiological remodeling in hypertrophy and heart failure predisposes the heart to lethal arrhythmias, which account for half of the mortality (1, 2). Experimental evidence derived from large scale clinical trials shows that inhibition of angiotensin II synthesis by inhibitors of angiotensin-converting enzyme or direct blockade of angiotensin receptor type 1 (AT1 1 receptor) with the antagonist losartan protects the heart from hypertensive complications (3, 4). A substantial reduction in mortality has been attributed to a significant decrease in sudden cardiac deaths possibly because of fewer episodes of complex arrhythmias (5, 6). The positive influence of inhibition of angiotensin-converting enzyme has been linked to bradykinin-mediated effects (7,8). However, the role of direct blockade of the AT1 receptor by losartan in episodes of sudden cardiac arrhythmias is still debated (9 -11). Electrophysiologic remodeling affects the entire spectrum of cardiac ion channels including the transient outward potassium current (I to ) whose density is often decreased in heart failure (2, 12, 13).The mechanism of I to down-regulation in heart failure is not completely understood and is likely to have multiple etiologies. In part it can be explained by the inhibitory effects of angiotensin II. Experiments with spontaneously hypertensive rats suggest that the AT1 receptor might be directly involved in the regulation of I to . In this animal model I to is inhibited and can be recovered by treatment with the AT1 receptor specific antagonist losartan (14). Experiments with isolated cardiomyocytes show that stimulation of the AT1 receptor results in the inhibition of I to in myocytes from rat or canine ventricle (15,16). In large mammals such as dogs or humans with substantial ventricular wall thickness, I to exhibits a transmural gradient that is vital for normal electrical activity (17,18). Distortion of the I to gradient leads to dispersion of repolarization across the ventricular wall, providing a substrate for ventricular arrhythmias (19). In both canine and human ventricle, I to density is higher in epicardial and midmyocardial than in the endocardial cells (17,18). The gradient of I to inversely correlates with the gradient of angiotensinogen across the ventricular wall whose expression is more prominent in the subendocardial than in either midmyocardium or epicardium regions (20). Evidence exists that cardiomyocytes, Purkinje fibers, and cardiac fibroblasts produce angiotensin II (21-23). Therefore, locally produced angiotensin II could act in a paracrine and/or autocrine manner to regulate I to . Experiments in vitro show that losartan stimulates I to in canine cardiomyocytes isolated from endocardium and converts the configuration of the action potential of endocar...

show abstract

Section: Resultssupporting

confidence: 49%

mentioning

confidence: 99%

Angiotensin Receptor Type 1 Forms a Complex with the Transient Outward Potassium Channel Kv4.3 and Regulates Its Gating Properties and Intracellular Localization

Doronin

Potapova

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It has been recognized early on that, with the exception of the KChIP4a splice variant, complex formation with KChIPs promotes the trafficking of Kv4 channels to the plasma membrane and increases their stability [1,70,79]. It was suspected that some ER retention motif within the Kv4 N-terminus is masked, and thus rendered ineffective, during Kv4/KChIP complex formation [70,79].…”

Section: Ca2+ Dependence Of Kv4/kchip Complex Formation and Membrane mentioning

confidence: 99%

“…It was suspected that some ER retention motif within the Kv4 N-terminus is masked, and thus rendered ineffective, during Kv4/KChIP complex formation [70,79]. In such a scenario Ca 2+ -sensitive KChIP binding to the Kv4 N-terminus (see above) would also confer Ca 2+ sensitivity to channel trafficking.…”

Section: Ca2+ Dependence Of Kv4/kchip Complex Formation and Membrane mentioning

confidence: 99%

“…The KChIP4a splice variant is special in various respects: Coexpression of KChIP4a does not lead to increased Kv4 channel surface expression [79] and leaves the voltage dependence of steady-state inactivation and the kinetics of recovery from inactivation unaffected. However, KChIP4a completely suppresses the fast macroscopic inactivation of Kv4 channels, resulting in delayed rectifier-like currents [15].…”

Section: Ca2+ Dependence Of Kv4/kchip Complex Formation and Membrane mentioning

confidence: 99%

See 1 more Smart Citation

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Bähring

2018

Channels

View full text Add to dashboard Cite

Kv channel-interacting proteins (KChIPs) belong to the neuronal calcium sensor (NCS) family of Ca2+-binding EF-hand proteins. KChIPs constitute a group of specific auxiliary β-subunits for Kv4 channels, the molecular substrate of transient potassium currents in both neuronal and non-neuronal tissues. Moreover, KChIPs can interact with presenilins to control ER calcium signaling and apoptosis, and with DNA to control gene transcription. Ca2+ binding via their EF-hands, with the consequence of conformational changes, is well documented for KChIPs. Moreover, the Ca2+ dependence of the presenilin/KChIP complex may be related to Alzheimer’s disease and the Ca2+ dependence of the DNA/KChIP complex to pain sensing. However, only in few cases could the Ca2+ binding to KChIPs be directly linked to the control of excitability in nerve and muscle cells known to express Kv4/KChIP channel complexes. This review summarizes current knowledge about the Ca2+ binding properties of KChIPs and the Ca2+ dependencies of macromolecular complexes containing KChIPs, including those with presenilins, DNA and especially Kv4 channels. The respective physiological or pathophysiolgical roles of Ca2+ binding to KChIPs are discussed.

show abstract

Voltage‐Gated Ion Channels

Fay

Haddick

Jan

2007

Handbook of Contemporary Neuropharmacology

View full text Add to dashboard Cite

This review will give an overview of the current state of knowledge about the structures of ion channels; the mechanisms of selectivity and gating; the cell biology of ion channels, including coassembly of channel subunits with other proteins and trafficking of ion channels; the physiological functions of ion channels and their roles in disease; and pharmacological tools available for the manipulation of ion channels in vitro and in vivo. While a vast array of ion channels exist with different selectivities and mechanisms of activation, some of these channel classes are reviewed in other chapters of this edition, and this chapter will focus on voltage‐gated K + , Na + , and Ca 2+ channels.

show abstract

A Fundamental Role for KChIPs in Determining the Molecular Properties and Trafficking of Kv4.2 Potassium Channels

Cited by 234 publications

References 59 publications

Angiotensin Receptor Type 1 Forms a Complex with the Transient Outward Potassium Channel Kv4.3 and Regulates Its Gating Properties and Intracellular Localization

Angiotensin Receptor Type 1 Forms a Complex with the Transient Outward Potassium Channel Kv4.3 and Regulates Its Gating Properties and Intracellular Localization

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Voltage‐Gated Ion Channels

Contact Info

Product

Resources

About