A modified local control model for Ca2+ transients in cardiomyocytes: Junctional flux is accompanied by release from adjacent non-junctional RyRs

Natalia S. Torres, Frank B. Sachse, Leighton T Izu, Joshua I. Goldhaber, Kenneth W. Spitzer, John H. Bridge

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Excitation-contraction coupling in cardiomyocytes requires Ca2+ influx through dihydropyridine receptors in the sarcolemma, which gates Ca2+ release through sarcoplasmic ryanodine receptors (RyRs). Ca2+ influx, release and diffusion produce a cytosolic Ca2+ transient. Here, we investigated the relationship between Ca2+ transients and the spatial arrangement of the sarcolemma including the transverse tubular system (t-system). To accomplish this, we studied isolated ventricular myocytes of rabbit, which exhibit a heterogeneously distributed t-system. We developed protocols for fluorescent labeling and triggered two-dimensional confocal microscopic imaging with high spatiotemporal resolution. From sequences of microscopic images, we measured maximal upstroke velocities and onset times of local Ca2+ transients together with their distance from the sarcolemma. Analyses indicate that not only sarcolemmal release sites, but also those that are within 1μm of the sarcolemma actively release Ca2+. Our data also suggest that release does not occur at sites further than 2.5μm from the sarcolemma. The experimental data are in agreement with results from a mathematical model of Ca2+ release and diffusion. Our findings can be explained by a modified local control model, which constrains the region of regenerative activation of non-junctional RyR clusters. We believe that this model will be useful for describing excitation-contraction coupling in cardiac myocytes with a sparse t-system, which includes those from diseased heart tissue as well as atrial myocytes of some species.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume68
DOIs
StatePublished - Mar 2014

Keywords

  • Calcium release
  • Cardiac myocyte
  • Excitation-contraction coupling
  • Sarcolemma
  • Transverse tubular system

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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