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Updated: Jul 29, 2025

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
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Slowly activating voltage-gated potassium current potentiation by ML277 is a novel cardioprotective intervention

Sean Brennan1, Abrar I M Alnaimi1, Lauren R McGuinness1

  • 1Department of Cardiovascular and Metabolic Medicine & Liverpool Centre for Cardiovascular Sciences, Institute of Life Course and Medical Sciences, University of Liverpool, L69 3GE, L7 8TX, UK.

PNAS Nexus
|May 26, 2023
PubMed

Insights

ML277, a slowly activating potassium current (IKs) potentiator, offers cardioprotection against ischemia. This compound improved cell survival and reduced infarct size, suggesting therapeutic potential for acute coronary syndromes.

Area of Science:

  • Cardiology
  • Pharmacology
  • Molecular Biology

Background:

  • Cardiovascular diseases cause a third of global deaths.
  • Ischemic heart disease, including myocardial infarction, results in 1.7 million deaths annually.
  • Effective cardioprotective interventions against ischemia are urgently needed.

Purpose of the Study:

  • To investigate the cardioprotective effects of ML277, a novel IKs potentiator.
  • To determine if ML277 can mitigate ischemia-reperfusion injury in cardiac models.

Main Methods:

  • Utilized cellular and whole-heart models of metabolic inhibition and reperfusion.
  • Assessed contractile recovery and cell survival.
  • Evaluated infarct size reduction using an ex vivo Langendorff model.

Main Results:

  • ML277 demonstrated significant cardioprotection across multiple models.
  • Increased contractile recovery and cell survival were observed with ML277 treatment.
  • ML277 reduced infarct size, even when administered during reperfusion.

Conclusions:

  • Potentiation of the slowly activating potassium current (IKs) with ML277 confers significant cardioprotection.
  • The protective effects of ML277 are comparable to ischemic preconditioning.
  • IKs potentiation represents a promising therapeutic strategy for acute coronary syndromes.

Keywords:
KCNQ1 (Kv7.1)/KCNE1cardioprotectionischemic protectionmyocardial infarctionslowly activating voltage-gated potassium current (IKs)

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