Related Experiment Video

Updated: Aug 22, 2025

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

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Acute Glycogen Synthase Kinase-3 Inhibition Modulates Human Cardiac Conduction

Gang Li1,2, Brittany D Brumback1,2, Lei Huang1

  • 1Department of Medicine, Cardiovascular Division, Washington University School of Medicine in St. Louis, Missouri, USA.

JACC. Basic to Translational Science
|November 7, 2022
PubMed

Insights

Glycogen synthase kinase 3 (GSK-3) inhibition acutely reduces cardiac conduction velocity in human tissue. This GSK-3 inhibition may increase arrhythmia risk, suggesting careful monitoring is needed.

Area of Science:

  • Cardiovascular physiology
  • Molecular cardiology
  • Pharmacology

Background:

  • Glycogen synthase kinase 3 (GSK-3) is a therapeutic target for various diseases, including cancer.
  • The specific role of GSK-3 in regulating human cardiac electrophysiology is not well understood.

Purpose of the Study:

  • To investigate the effects of GSK-3 inhibition on human cardiac electrophysiology.
  • To elucidate the underlying mechanisms of GSK-3 inhibition-induced electrophysiological changes.

Main Methods:

  • Utilized human cardiac slices to assess electrophysiological parameters.
  • Employed SB216763, a specific GSK-3 inhibitor.
  • Integrated computational modeling with experimental data.

Main Results:

  • GSK-3 inhibition with SB216763 acutely reduced conduction velocity in human cardiac slices.
  • Mechanistic insights revealed decreased sodium-channel conductance and tissue conductivity.
  • These changes may underlie the observed electrophysiological alterations.

Conclusions:

  • GSK-3 inhibition alters human myocardial electrophysiology.
  • This alteration may create an arrhythmogenic substrate.
  • Monitoring for adverse pro-arrhythmic events is recommended during GSK-3 inhibition therapy.
Keywords:
ABC, active β-cateninAPD, action potential durationBDM, 2,3-butanedione monoximeCV, conduction velocityCx43, connexin 43GNa, sodium-channel conductanceGOF, gain of functionGSK-3 inhibitorGSK-3, glycogen synthase kinase 3INa, sodium currentLV, left ventricleNaV1.5, pore-forming α-subunit protein of the voltage-gated cardiac sodium channelPCR, polymerase chain reactionRMP, resting membrane potentialRT-qPCR, reverse transcription-quantitative polymerase chain reactionSB2, SB216763SB216763cDNA, complementary DNAdVm/dtmax, maximum upstroke velocityelectrophysiologyhuman cardiac slices

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