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Calcium Sparks and Excitation–Contraction Coupling in Phospholamban‐Deficient Mouse Ventricular Myocytes
Author(s) -
Santana L. F.,
Kranias E. G.,
Lederer W. J.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.021bi.x
Subject(s) - phospholamban , myocyte , chemistry , biophysics , coupling (piping) , calcium , excitation–contraction coupling , contraction (grammar) , intracellular , endoplasmic reticulum , medicine , analytical chemistry (journal) , biochemistry , biology , materials science , chromatography , organic chemistry , metallurgy
1 We examined [Ca 2+ ] i and L‐type Ca 2+ channel current ( I Ca ) in single cardiac myocytes to determine how the intracellular protein phospholamban (PLB) influences excitation‐contraction (E–C) coupling in heart. Wild type (WT) and PLB‐deficient (KO) mice were used. Cells were patch clamped in whole–Cell mode while [Ca 2+ ] i was imaged simultaneously using the Ca 2+ indicator fluo‐3 and a confocal microscope. 2 Although I Ca was similar in magnitude, the decay of I Ca was faster in KO than in WT cells and the [Ca 2+ ] i transient was larger and decayed faster. Furthermore, the E–C coupling ‘gain’ (measured as Δ[Ca 2+ ] i / I Ca ) was larger in KO cells than in WT cells. 3 Spontaneous Ca 2+ sparks were three times more frequent and larger in KO cells than in WT myocytes but, surprisingly, the time constants of decay were similar. 4 SR Ca 2+ content was significantly greater in KO than in WT cells. When the SR Ca 2+ content in KO cells was reduced to that in WT cells, Ca 2+ sparks in these ‘modified’ (KO') cells decayed faster. E–C coupling gain, [Ca 2+ ] i transient amplitude and the kinetics of decay of I Ca were similar in KO' and WT cells. 5 We conclude that SR Ca 2+ content influences (1) I Ca , (2) the amplitude and kinetics of Ca 2+ sparks and [Ca 2+ ] i transients, (3) the sensitivity of the RyRs to triggering by [Ca 2+ ] i , (4) the amount of Ca 2+ released, (5) the magnitude of the E–C coupling ‘gain’ function, and (6) the rate of Ca 2+ re‐uptake by the SR Ca 2+ ‐ATPase. In KO cells, the larger [Ca 2+ ] i transients and Ca 2+ sparks speed up I Ca inactivation. Finally, we conclude that PLB plays an important regulatory role in E–C coupling by modulating SR Ca 2+ ‐ATPase activity, which establishes the SR Ca 2+ content and consequently influences the characteristics of local and global Ca 2+ signalling.