Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2

Benito-Bueno, Angela de; Socuéllamos, Paula G.; Merinero, Yaiza G.; Cercós, Pilar; Izquierdo, Carolina; Daniel-Mozo, Miguel; Marín-Olivero, Irene; Pérez-Lara, Ángel; González‐Vera, Juan A.; Orte, Ángel; Albert, Armando; Martı́n-Martı́nez, Mercedes; Gutiérrez-Rodríguez, Marta; Valenzuela, Carmen

doi:10.3390/ijms23169170

Cited by 3 publications

(2 citation statements)

References 49 publications

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“…They also identified IQM-266 as a novel KChIP3 ligand with similar inhibitory properties to IQM-PC330 and IQM-PC332 [64]. Recently, IQM-266 was reported to bind KChIP2 and increase KV4.3/KChIP2 currents [65].…”

Section: Kchip Ligands Affect Kchip Regulation On Kv4mentioning

confidence: 95%

KV Channel-Interacting Proteins in Neurological and Cardiovascular System: An Updated Review

Wu¹,

Song²,

Zhang³

et al. 2023

Preprint

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KV channel-interacting proteins (KChIPs) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. As the auxiliary subunit, KChIPs are critically involved in regulating the amplitude and gating properties of KV4 channels by modulating their cell surface trafficking, voltage-dependent activation, inactivation kinetics, and recovery rate from inactivation. IKs, ICa,L, and INa can also be regulated by KChIPs. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the KV4 currents. Interestingly, all KChIPs can act as transcription factors to control the expression of genes involved in pain, memory, and circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of many diseases, such as arrhythmia, heart failure, Alzheimer's disease, etc. In this review, we summarize the research progress of KChIPs in their structural properties, physiological functions, and pathological roles in disease progression, and provide an overview of the therapeutic potential of KChIPs as pharmacological targets for associated disorders.

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Section: Kchip Ligands Affect Kchip Regulation On Kv4mentioning

confidence: 95%

KV Channel-Interacting Proteins in Neurological and Cardiovascular System: An Updated Review

Wu¹,

Song²,

Zhang³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…They also identified IQM-266 as a novel KChIP3 ligand with similar inhibitory properties to IQM-PC330 and IQM-PC332 [76]. Recently, IQM-266 was reported to bind KChIP2 and increase K V 4.3/KChIP2 currents [77].…”

Section: Role Of Kchips In Regulating Other Ion Channelsmentioning

confidence: 95%

KV Channel-Interacting Proteins in the Neurological and Cardiovascular Systems: An Updated Review

Song

Zhang

et al. 2023

Cells

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KV channel-interacting proteins (KChIP1-4) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the fast inactivating-KV4 currents. As the auxiliary subunit, KChIPs are critically involved in regulating the surface protein expression and gating properties of KV4 channels. Mechanistically, KChIP1, KChIP2, and KChIP3 promote the translocation of KV4 channels to the cell membrane, accelerate voltage-dependent activation, and slow the recovery rate of inactivation, which increases KV4 currents. By contrast, KChIP4 suppresses KV4 trafficking and eliminates the fast inactivation of KV4 currents. In the heart, IKs, ICa,L, and INa can also be regulated by KChIPs. ICa,L and INa are positively regulated by KChIP2, whereas IKs is negatively regulated by KChIP2. Interestingly, KChIP3 is also known as downstream regulatory element antagonist modulator (DREAM) because it can bind directly to the downstream regulatory element (DRE) on the promoters of target genes that are implicated in the regulation of pain, memory, endocrine, immune, and inflammatory reactions. In addition, all the KChIPs can act as transcription factors to repress the expression of genes involved in circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of several neurological and cardiovascular diseases. For example, KChIP2 is decreased in failing hearts, while loss of KChIP2 leads to increased susceptibility to arrhythmias. KChIP3 is increased in Alzheimer’s disease and amyotrophic lateral sclerosis, but decreased in epilepsy and Huntington’s disease. In the present review, we summarize the progress of recent studies regarding the structural properties, physiological functions, and pathological roles of KChIPs in both health and disease. We also summarize the small-molecule compounds that regulate the function of KChIPs. This review will provide an overview and update of the regulatory mechanism of the KChIP family and the progress of targeted drug research as a reference for researchers in related fields.

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The Multifunctional Role of KCNE2: From Cardiac Arrhythmia to Multisystem Disorders

Song,

Zhuge,

et al. 2024

Cells

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The KCNE2 protein is encoded by the kcne2 gene and is a member of the KCNE protein family, also known as the MinK-related protein 1 (MiRP1). It is mostly present in the epicardium of the heart and gastric mucosa, and it is also found in the thyroid, pancreatic islets, liver and lung, among other locations, to a lesser extent. It is involved in numerous physiological processes because of its ubiquitous expression and partnering promiscuity, including the modulation of voltage-dependent potassium and calcium channels involved in cardiac action potential repolarization, and regulation of secretory processes in multiple epithelia, such as gastric acid secretion, thyroid hormone synthesis, generation and secretion of cerebrospinal fluid. Mutations in the KCNE2 gene or aberrant expression of the protein may play a critical role in cardiovascular, neurological, metabolic and multisystem disorders. This article provides an overview of the advancements made in understanding the physiological functions in organismal homeostasis and the pathophysiological consequences of KCNE2 in multisystem diseases.

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Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2

Cited by 3 publications

References 49 publications

KV Channel-Interacting Proteins in Neurological and Cardiovascular System: An Updated Review

KV Channel-Interacting Proteins in Neurological and Cardiovascular System: An Updated Review

KV Channel-Interacting Proteins in the Neurological and Cardiovascular Systems: An Updated Review

The Multifunctional Role of KCNE2: From Cardiac Arrhythmia to Multisystem Disorders

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