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Updated: Jul 29, 2025

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

Published on: July 3, 2013

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Calcium- and voltage-driven atrial alternans: Insight from [Ca]i and Vm asynchrony

G Kanaporis1, E Martinez-Hernandez1, L A Blatter1

  • 1Department of Physiology & Biophysics, Rush University Medical Center, Chicago, Illinois, USA.

Physiological Reports
|May 25, 2023
PubMed

Insights

Cardiac alternans, beat-to-beat changes in contraction and electrical activity, are primarily driven by intracellular calcium (Ca) handling, not membrane voltage (Vm) changes. This calcium-driven mechanism influences cardiac function and excitation-contraction coupling.

Area of Science:

  • Cardiology
  • Biophysics
  • Molecular and Cellular Biology

Background:

  • Cardiac alternans involve beat-to-beat alternations in contraction strength, action potential duration (APD), and intracellular calcium transient (CaT) amplitude.
  • Excitation-contraction coupling relies on coupled membrane voltage (Vm) and intracellular calcium (Ca) dynamics.
  • Alternans are classified as Vm-driven or Ca-driven based on the primary regulatory disturbance.

Purpose of the Study:

  • To determine the primary driver of pacing-induced cardiac alternans in rabbit atrial myocytes.
  • To investigate the interplay between Vm and Ca regulation in the development of alternans.
  • To elucidate the independent and coupled dynamics of APD and CaT alternans.

Main Methods:

  • Combined patch clamp and fluorescence measurements of intracellular Ca and Vm.
  • Utilized alternans AP voltage clamp protocols with extra action potentials (APs).
  • Examined electrically coupled cell pairs to assess alternans synchrony and regulation.

Main Results:

  • APD and CaT alternans are often synchronized but can exhibit uncoupled behavior, indicating partial independence.
  • Extra APs frequently failed to override pre-existing CaT alternans, supporting a Ca-driven mechanism.
  • Dyssynchrony in electrically coupled cells suggests autonomous regulation of CaT alternans.

Conclusions:

  • Evidence supports Ca-driven cardiac alternans as the predominant mechanism in rabbit atrial myocytes.
  • While Ca dynamics appear primary, the intricate coupling of Vm and Ca regulation prevents complete independence of APD and CaT alternans.
  • Understanding these dynamics is crucial for comprehending cardiac arrhythmogenesis.

Keywords:
atrial myocytecardiac alternansexcitation-contraction couplingintracellular [Ca]imembrane potential

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