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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

Hysteresis effect implicates calcium cycling as a mechanism of repolarization alternans

Mariah L Walker1, Xiaoping Wan, Glenn E Kirsch

  • 1Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Hamman 330, Cleveland, Ohio 44109-1998, USA.

Circulation
|October 29, 2003
PubMed

Insights

T-wave alternans hysteresis, a phenomenon where alternans persist after heart rate slows, is an intrinsic cardiac myocyte property. This suggests intracellular calcium cycling is key to alternans mechanisms and sudden cardiac death risk.

Area of Science:

  • Cardiology
  • Electrophysiology
  • Cellular Biology

Background:

  • T-wave alternans, a marker of repolarization instability, is linked to sudden cardiac death.
  • A hysteresis effect, where T-wave alternans persist after heart rate reduction, has been observed in patients.

Purpose of the Study:

  • To investigate if T-wave alternans hysteresis is an intrinsic property of cardiac myocytes.
  • To explore the role of intracellular calcium cycling in the mechanism of alternans hysteresis.

Main Methods:

  • Langendorff-perfused guinea pig hearts were paced to induce alternans, with optical action potentials recorded.
  • Whole-cell patch-clamp electrophysiology was performed on isolated cardiac myocytes, with and without BAPTA-AM (calcium chelator).

Main Results:

  • Alternans hysteresis was consistently observed in isolated hearts, with alternans persisting at significantly lower heart rates during deceleration.
  • Optical mapping revealed hysteresis in the threshold for spatially discordant alternans.
  • Calcium chelation with BAPTA-AM dose-dependently increased alternans threshold and inhibited hysteresis without affecting baseline action potential duration.

Conclusions:

  • Alternans hysteresis is an intrinsic property of cardiac myocytes.
  • This hysteresis can lead to persistent arrhythmogenic alternans even after heart rate normalization.
  • Intracellular calcium cycling plays a critical role in the mechanism underlying T-wave alternans.
Abstract

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