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The role of luminal Ca 2+ in the generation of Ca 2+ waves in rat ventricular myocytes
Author(s) -
Lukyanenko Valeriy,
Subramanian Saisunder,
Györke Inna,
Wiesner Theodore F.,
Györke Sandor
Publication year - 1999
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.1469-7793.1999.0173r.x
Subject(s) - thapsigargin , endoplasmic reticulum , extracellular , caffeine , biophysics , cytosol , chemistry , myocyte , ryanodine receptor , calcium , intracellular , stimulation , medicine , endocrinology , biology , biochemistry , enzyme , organic chemistry
1 We used confocal Ca 2+ imaging and fluo‐3 to investigate the transition of localized Ca 2+ releases induced by focal caffeine stimulation into propagating Ca 2+ waves in isolated rat ventricular myocytes. 2 Self‐sustaining Ca 2+ waves could be initiated when the cellular Ca 2+ load was increased by elevating the extracellular [Ca 2+ ] ([Ca 2+ ] o ) and they could also be initiated at normal Ca 2+ loads when the sensitivity of the release sites to cytosolic Ca 2+ was enhanced by low doses of caffeine. When we prevented the accumulation of extra Ca 2+ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self‐sustaining Ca 2+ waves on elevation of [Ca 2+ ] o . Inhibition of SR Ca 2+ uptake by thapsigargin in cells already preloaded with Ca 2+ above normal levels did not prevent local Ca 2+ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 %. Tetracaine (0·75 mM) caused transient complete inhibition of both local and propagating Ca 2+ signals, followed by full recovery of the responses due to increased SR Ca 2+ accumulation. 3 Computer simulations using a numerical model with spatially distinct Ca 2+ release sites suggested that increased amounts of releasable Ca 2+ might not be sufficient to generate self‐sustaining Ca 2+ waves under conditions of Ca 2+ overload unless the threshold of release site Ca 2+ activation was set at relatively low levels (< 1·5 μM). 4 We conclude that the potentiation of SR Ca 2+ release channels by luminal Ca 2+ is an important factor in Ca 2+ wave generation. Wave propagation does not require the translocation of Ca 2+ from the spreading wave front into the SR. Instead, it relies on luminal Ca 2+ sensitizing Ca 2+ release channels to cytosolic Ca 2+ .