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Updated: May 21, 2026

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

Transient outward K+ current reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp

A J Workman1, G E Marshall, A C Rankin

  • 1Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. antony.workman@glasgow.ac.uk

The Journal of Physiology
|June 27, 2012
PubMed

Insights

Reduced human atrial transient outward K(+) current (I(TO)) prolongs action potential duration and increases arrhythmia risk. Selective I(TO) modulation using dynamic clamp reveals its critical role in atrial electrophysiology and potential therapeutic targeting for arrhythmias.

Area of Science:

  • Cardiology
  • Electrophysiology
  • Computational Biology

Background:

  • Human atrial transient outward K(+) current (I(TO)) reduction is observed in cardiac pathologies.
  • The precise impact of I(TO) reduction on action potentials and arrhythmia mechanisms remains unclear due to limitations of non-selective blockers.

Purpose of the Study:

  • To investigate the effects of selective I(TO) modulation on atrial action potential (AP) shape and duration (APD).
  • To examine the influence of I(TO) changes on afterdepolarizations and abnormal automaticity under beta-adrenergic stimulation.
  • To utilize the dynamic-clamp technique for precise control of I(TO) in isolated atrial cells.

Main Methods:

  • Isolated human and rabbit atrial cells were utilized.
  • Whole-cell patch clamp recordings were performed at physiological temperature (35-37°C).
  • Dynamic-clamp simulations were employed to selectively reduce or block I(TO) and to increase I(TO).

Main Results:

  • Selective I(TO) reduction significantly slowed AP phase 1 and elevated the plateau, leading to prolonged APD in both human and rabbit atrial cells.
  • In human cells, I(TO) block increased APD(50), APD(90), and APD(-61 mV) (effective refractory period).
  • In rabbit cells, partial I(TO) block increased the incidence of cellular arrhythmic depolarizations (CADs) under isoproterenol (ISO) stimulation, which was reversible and suppressed by increased I(TO) or beta(1)-antagonism.

Conclusions:

  • Selective modulation of I(TO) using dynamic clamp alters atrial action potential characteristics and can induce or suppress arrhythmias.
  • These findings highlight the crucial role of I(TO) in maintaining normal atrial electrophysiology.
  • Targeting I(TO) presents a potential therapeutic strategy for managing atrial fibrillation and other cardiac arrhythmias.

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