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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

Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity

Emmanuel Camors1, Peter J Mohler, Donald M Bers

  • 1Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.

Journal of Molecular and Cellular Cardiology
|March 13, 2012
PubMed

Insights

Reduced Ankyrin-B (AnkB) function in heart cells increases calcium sparks and waves, raising the risk of arrhythmias. This occurs due to altered ion transport and coordinated RyR openings, not increased total SR calcium leak.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Electrophysiology

Background:

  • Ankyrin-B (AnkB) loss-of-function is linked to human ventricular arrhythmias and sudden cardiac death.
  • AnkB deficiency in cardiac myocytes affects key ion transporters like Na/Ca exchanger (NCX) and Na/K-ATPase (NKA), impacting intracellular sodium ([Na](i)) and calcium ([Ca](i)) regulation.
  • Understanding AnkB's role in cardiac calcium handling is crucial for preventing arrhythmias.

Purpose of the Study:

  • To investigate the effects of AnkB reduction on cardiac intracellular sodium ([Na](i)), calcium ([Ca](i)), and sarcoplasmic reticulum (SR) calcium release.
  • To determine the mechanisms underlying altered calcium handling and its contribution to arrhythmogenesis in AnkB-deficient myocytes.

Main Methods:

  • Comparison of cardiac myocytes from AnkB heterozygous (AnkB(+/-)) and wild-type (WT) mice.
  • Measurement of intracellular ion concentrations, calcium transients, SR calcium content, and SR calcium leak.
  • Analysis of spontaneous calcium sparks (CaSpF) and ryanodine receptor (RyR) activity in intact and permeabilized myocytes.

Main Results:

  • AnkB(+/-) myocytes exhibited reduced NCX and NKA transport function but maintained normal [Na](i) and diastolic [Ca](i).
  • Larger Ca transients, increased SR Ca content, and enhanced fractional SR Ca release were observed in AnkB(+/-) myocytes.
  • AnkB(+/-) myocytes showed a significantly higher frequency of spontaneous diastolic Ca sparks (CaSpF) due to more coordinated RyR openings, despite unaffected total SR Ca leak.

Conclusions:

  • AnkB reduction alters cardiac ion transport, leading to increased coupled RyR openings and more frequent Ca sparks and waves.
  • This altered calcium dynamics, specifically the bias towards Ca sparks, enhances the propensity for pro-arrhythmic events in AnkB(+/-) mice.
  • The findings highlight a novel mechanism by which AnkB deficiency promotes triggered arrhythmias through localized RyR regulation.

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