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Measuring Fast Calcium Fluxes in Cardiomyocytes
12:10

Measuring Fast Calcium Fluxes in Cardiomyocytes

Published on: November 29, 2011

Cellular mechanism of calcium-mediated triggered activity in the heart

Rodolphe P Katra1, Kenneth R Laurita

  • 1The Heart and Vascular Research Center, MetroHealth Campus, and the Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.

Circulation Research
|February 19, 2005
PubMed

Insights

Enhanced calcium entry causes spontaneous calcium release (SCR) from the sarcoplasmic reticulum, leading to triggered activity. SCR events near the endocardium initiate delayed afterdepolarizations and potentially polymorphic ventricular tachycardia under calcium overload.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Physiology

Background:

  • Calcium overload, driven by increased calcium entry, is implicated in spontaneous calcium release (SCR), delayed afterdepolarizations (DAD), and triggered activity.
  • The precise link between elevated intracellular calcium and the specific origin of triggered activity remains incompletely understood.

Purpose of the Study:

  • To investigate the mechanistic relationship between enhanced intracellular calcium levels and triggered activity.
  • To determine if elevated intracellular calcium leads to multiple SCR events and identify the initiating event for triggered beats.

Main Methods:

  • Utilized optical mapping of action potentials and ratiometric calcium transients.
  • Employed an electromechanically-uncoupled canine wedge model with enhanced calcium entry via I(Ks) blockade and beta-adrenergic stimulation.
  • Analyzed SCR events, calcium transients, and triggered activity under rapid pacing.

Main Results:

  • Enhanced calcium entry accelerated calcium uptake but increased endocardial cytoplasmic calcium during rapid pacing.
  • Rapid pacing induced multiple, simultaneous SCR events, predominantly originating near the endocardium with greater amplitude and earlier onset.
  • SCR events with the largest amplitude and earliest onset were identified as foci for DAD-mediated triggered activity.
  • Polymorphic ventricular tachycardia (VT) was observed in some experiments correlating with multiple SCR events.

Conclusions:

  • Multiple, simultaneous SCR events occur in regions with slower calcium uptake and elevated diastolic calcium.
  • Endocardial SCR events, characterized by larger amplitude and earlier onset, are more likely to initiate DAD-mediated triggered activity.
  • Multiple SCR events may represent a mechanism for polymorphic VT under conditions of calcium overload.

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