KCNE1

Last update 23 Jan 2025

Basic Info

Synonyms

Delayed rectifier potassium channel subunit IsK, IKs producing slow voltage-gated potassium channel subunit beta Mink, IsK

+ [7]

Introduction

Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:19219384). Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr).

100 Clinical Results associated with KCNE1

100 Translational Medicine associated with KCNE1

0 Patents (Medical) associated with KCNE1

1,023

Literatures (Medical) associated with KCNE1

01 Feb 2025·British Journal of Pharmacology

Dual effects of mefenamic acid on the I_Ks molecular complex

Article

Author: Sahakyan, Harutyun ; Eldstrom, Jodene ; Chan, Magnus ; Pourrier, Marc ; Fedida, David ; Vardanyan, Vitya

AbstractBackground and PurposeMutations in both KCNQ1 and KCNE1, which together form the cardiac IKs current, are associated with inherited conditions such as long and short QT syndromes. Mefenamic acid, a non‐steroidal anti‐inflammatory drug, is an IKs potentiator and may be utilised as an archetype to design therapeutically useful IKs agonists. However, here we show that mefenamic acid can also act as an IKs inhibitor, and our data reveal its dual effects on KCNQ1/KCNE1 channels.Experimental ApproachEffects of mefenamic acid on wild type (WT) and mutant KCNQ1/KCNE1 channels expressed in tsA201 cells were studied using whole cell patch clamp. Molecular dynamics simulations were used to determine trajectory clustering.Key ResultsMefenamic acid inhibits WT IKs at high concentrations while preserving some attributes of current potentiation. Inhibitory actions of mefenamic acid are unmasked at lower drug concentrations by KCNE1 and KCNQ1 mutations in the mefenamic acid binding pocket, at the extracellular end of KCNE1 and in the KCNQ1 S6 helix. Mefenamic acid does not inhibit KCNQ1 in the absence of KCNE1 but inhibits IKs current in a concentration‐dependent manner in the mutant channels. Inhibition involves modulation of pore kinetics and/or voltage sensor domain‐pore coupling in WT and in the KCNE1 E43C mutant.Conclusion and ImplicationsThis work highlights the importance of structural motifs at the extracellular inter‐subunit interface of KCNQ1 and KCNE1 channels, and their interactions, in determining the nature of drug effects on the IKs channel complex and has important implications for treating patients with specific long QT mutations.

07 Jan 2025·Combinatorial Chemistry & High Throughput Screening

Integrated Network Pharmacology and Transcriptomics Analysis to Elucidate the Mechanism of Huoxue Tongluo Qiwei Decoction in the Treatment of Erectile Dysfunction in Spontaneously Hypertensive Rats through Angii-Activated Pkcε Pathway

Article

Author: Zhao, Cong ; Wang, Bin ; Zou, Kali ; Feng, Junlong ; Deng, Sheng ; Li, Haisong ; Wang, Jisheng

Background and Aim:As a classical formula to invigorate blood circulation, Huoxue Tongluo Qiwei Decoction (HTQD) can effectively treat hypertensive erectile dysfunction (ED), but its exact mechanism of action is not yet clear. The goal of this research was to explore the potential mechanism of HTQD in improving hypertensive erectile dysfunction in rats through transcriptomics, network pharmacology, and associated animal experimentations.Methods:The HTQD chemical constituents were screened using high-performance liquid chromatography- tandem mass spectrometry (HPLC-MS/MS). Furthermore, transcriptomics analysis was performed via mRNA sequencing to identify significantly differentially expressed proteins. Moreover, the key target proteins of HTQD in the treatment of hypertensive ED were screened by network pharmacology and transcriptomics. In addition, the endothelial cells of the corpus cavernosum were assessed using hematoxylin-eosin staining. The transcript and protein expressions were evaluated via western blotting and Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results:The network pharmacology and transcriptome mRNA sequencing revealed that KCNE1 may be the target protein of HTQD in improving hypertensive ED. After HTQD treatment, the systolic and diastolic blood pressure (BP) of hypertensive rats decreased, the number of erections increased, and the pathological structure of the penis was improved. Moreover, HTQD downregulated the protein and mRNA expression of AngII, AT1R, DAG, and PKCε, whereas it upregulated the transcript and protein expression of KCNE1.Conclusion:HTQD may activate the PKCε pathway through AngII, inhibit the expression of KCNE1 protein, relax vascular smooth muscles, and improve erectile function.

31 Dec 2024·Channels

The endocannabinoid ARA-S facilitates the activation of cardiac Kv7.1/KCNE1 channels from different species

Article

Author: Linhart, Veronika A. ; Hiniesto-Iñigo, Irene ; Liin, Sara I. ; Kusay, Ali S.

The endogenous endocannabinoid-like compound N-arachidonoyl-L-serine (ARA-S) facilitates activation of the human Kv7.1/KCNE1 channel and shortens a prolonged action potential duration and QT interval in guinea pig hearts. Hence, ARA-S is interesting to study further in cardiac models to explore the functional impact of such Kv7.1/KCNE1-mediated effects. To guide which animal models would be suitable for assessing ARA-S effects, and to aid interpretation of findings in different experimental models, it is useful to know whether Kv7.1/KCNE1 channels from relevant species respond similarly to ARA-S. To this end, we used the two-electrode voltage clamp technique to compare the effects of ARA-S on Kv7.1/KCNE1 channels from guinea pig, rabbit, and human Kv7.1/KCNE1, when expressed in Xenopus laevis oocytes. We found that the activation of Kv7.1/KCNE1 channels from all tested species was facilitated by ARA-S, seen as a concentration-dependent shift in the voltage-dependence of channel opening and increase in current amplitude and conductance over a broad voltage range. The rabbit channel displayed quantitatively similar effects as the human channel, whereas the guinea pig channel responded with more prominent increase in current amplitude and maximal conductance. This study suggests that rabbit and guinea pig models are both suitable for studying ARA-S effects mediated via Kv7.1/KCNE1.

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KCNE1

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