Spatiotemporal characteristics of SR Ca2+ uptake and release in detubulated rat ventricular myocytes

Fabien Brette, Sanda Despa, Donald M Bers, Clive H. Orchard

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

In cardiac ventricular myocytes, sarcoplasmic reticulum (SR) Ca 2+ load is a key determinant of SR Ca2+ release. This release normally occurs predominantly from SR junctions at sarcolemmal invaginations (t-tubules), ensuring synchronous SR Ca2+ release throughout the cell. However under conditions of Ca2+ overload, spontaneous SR Ca2+ release and propagating Ca2+ waves can occur, which are pro-arrhythmic. We used detubulated rat ventricular myocytes to determine the dependence of Ca2+ wave propagation on SR Ca 2+ load, and the role of t-tubules in SR Ca2+ uptake and spontaneous release. After SR Ca2+ depletion, recovery of Ca 2+ transient amplitude (and SR Ca2+ load) was slower in detubulated than control myocytes (half-maximal recovery: 9.9 ± 1.4 vs. 5.5 ± 0.7:beats). In detubulated myocytes the extent and velocity of Ca2+ propagation from the cell periphery increased with each beat and depended steeply on SR Ca2+ load. Isoproterenol (ISO) accelerated recovery, increased maximal propagation velocity and reduced the threshold SR Ca2+ load for propagation. Ca2+ spark frequency was uniform across control cell width and was similar at the periphery of detubulated cells. However, internal Ca2+ spark frequency in detubulated cells was 75% lower (despite comparable local SR Ca2+ load); this transverse spark frequency profile was similar to that in atrial myocytes. We conclude that: (1) t-tubule Ca2+ fluxes normally control SR Ca2+ refilling; (2) Ca2+ wave propagation depends steeply on SR Ca2+ content (3) SR-t-tubule junctions are important in initiating SR Ca2+ release and (4) ISO enhances propagation of SR Ca release, but not the initiation of SR Ca release events (for given SR Ca 2+ loads).

Original languageEnglish (US)
Pages (from-to)804-812
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume39
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

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Keywords

  • Calcium
  • Cardiac myocytes
  • Sarcoplasmic reticulum
  • t-tubules

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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