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March 14, 2025British Journal of PharmacologyOpen Access

Rescue of loss‐of‐function long QT syndrome‐associated mutations in KV7.1/KCNE1 by the endocannabinoid N‐arachidonoyl‐L‐serine (ARA‐S)

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Why the study?

Mutations in KV7.1/KCNE1 causing channel loss-of-function frequently lead to congenital long QT syndrome. The study examined whether the endocannabinoid ARA-S can facilitate activation of LQTS-associated mutated channels across various channel regions and counteract loss-of-function.

Population

Xenopus oocytes expressing human KV7.1/KCNE1 with 20 LQTS type 1-associated mutations, mammalian cells, and cardiomyocytes

Comparison

Effects of ARA-S across mutated channels

Design

Preclinical in vitro electrophysiology study

Key result

ARA-S enhanced the function of 20 LQTS type 1-associated mutated channels by shifting V50 and increasing current amplitude, and shortened the action potential duration in cardiomyocytes.

Authors

IHIrene Hiniesto‐IñigoASAkshay SridharJLJulien Louradour

Discussion

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Member takes

Overview

Supports targeted LQTS type 1 therapy development; leaves open translation from animal models to patients.

Structured PICO

P
Population
Xenopus oocytes expressing human KV7.1/KCNE1 channels with 20 LQTS type 1-associated mutations, and mammalian cells/cardiomyocytes
I
Intervention
N-arachidonoyl-L-serine (ARA-S)
O
Outcome
Channel activation (shift in V50 and increase in current amplitude) and action potential durationsurrogate

ARA-S rescues loss-of-function in diverse LQTS type 1-associated KV7.1/KCNE1 mutations, highlighting its potential for developing targeted therapies for long QT syndrome.

Cite This Study

Hiniesto‐Iñigo et al. (2025) studied Congenital long QT syndrome (LQTS). N-arachidonoyl-L-serine (ARA-S) was evaluated on Channel function (V50 and current amplitude). ARA-S enhanced the function of 20 LQTS type 1-associated mutated channels by shifting V50 and increasing current amplitude, and shortened the action potential duration in cardiomyocytes.

synapsesocial.com/papers/6a10257efb2817e31dfcf4abhttps://doi.org/10.1111/bph.70008
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The endocannabinoid ARA-S acts as an endogenous rescuing factor of Kv7.1/KCNE1 carrying Long QT syndrome mutations and paves the way for drug development strategies2024
  2. 2Endocannabinoids enhance hKV7.1/KCNE1 channel function and shorten the cardiac action potential and QT interval2023 · 12 citations
  3. 3Pharmacological rescue of specific long QT variants of KCNQ1/KCNE1 channels2022 · 7 citations
  4. 4Pharmacological Activation of Normal and Arrhythmia-Associated Mutant KCNQ1 Potassium Channels2003 · 96 citations
  5. 5Long QT 1 Mutation KCNQ1A344VIncreases Local Anesthetic Sensitivity of the Slowly Activating Delayed Rectifier Potassium Current2006 · 29 citations