Spatial Distribution of Calcium Sparks Determines Their Ability to Induce Afterdepolarizations in Human Atrial Myocytes

C. Tarifa, A. Vallmitjana, V. Jiménez-Sábado, M. Marchena, A. Llach, A. Herraiz-Martínez, Hector Godoy-Marín, C. Nolla-Colomer, Antonino Ginel, Xavier Viñolas, Jose Montiel, Francisco Ciruela, B. Echebarria, R. Benítez, Juan Cinca, Leif Hove-Madsen

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Analysis of the spatio-temporal distribution of calcium sparks showed a preferential increase in sparks near the sarcolemma in atrial myocytes from patients with atrial fibrillation (AF), linked to higher ryanodine receptor (RyR2) phosphorylation at s2808 and lower calsequestrin-2 levels. Mathematical modeling, incorporating modulation of RyR2 gating, showed that only the observed combinations of RyR2 phosphorylation and calsequestrin-2 levels can account for the spatio-temporal distribution of sparks in patients with and without AF. Furthermore, we demonstrate that preferential calcium release near the sarcolemma is key to a higher incidence and amplitude of afterdepolarizations in atrial myocytes from patients with AF.
Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalJACC: Basic to Translational Science
Volume8
Issue number1
DOIs
Publication statusPublished - 2023

Keywords

  • AF, atrial fibrillation
  • Csq-2, cardiac calsequestrin (type 2)
  • ICa, calcium current
  • ITI, transient inward current
  • NCX-1, cardiac Na+/Ca2+ exchanger (type 1)
  • PLB, phospholamban
  • RyR2, cardiac ryanodine receptor (type 2)
  • SERCA2a, cardiac sarcoplasmic reticulum Ca-ATPase pump protein (type 2)
  • SR, sarcoplasmic reticulum
  • atrial fibrillation
  • human atrial myocyte
  • ryanodine receptor
  • sarcoplasmic reticulum
  • transient inward currents

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