Key result
Histamine application in HeLa cells evoked a hierarchy of Ca2+ signaling events, from fundamental blips to intermediate puffs to global Ca2+ waves, analogous to signaling in cardiac muscle cells.
The study demonstrates a hierarchical Ca2+ signaling system in HeLa cells, from blips to puffs to waves, which is analogous to signaling in cardiac muscle cells.
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Elementary Ca2+ blips/puffs mapped in non-excitable cells; leaves open in vivo roles and clinical translation.
Confocal microscopy was used to investigate hormone-induced subcellular Ca2+ release signals from the endoplasmic reticulum (ER) in a prototype non-excitable cell line (HeLa cells). 2. Histamine application evoked two types of elementary Ca2+ signals: (i) Ca2+ blips arising from single ER Ca2+ release channels (amplitude, 30 nM; lateral spreading, 1.3 microns); (ii) Ca2+ puffs resulting from the concerted activation of several Ca2+ blips (amplitude, 170 nM; spreading, 4 microns). 3. Ca2+ waves in the HeLa cells arose from a variable number of initiation sites, but for individual cells, the number and subcellular location of the initiation sites were constant. The kinetics and amplitude of global Ca2+ signals were directly proportional to the number of initiation sites recruited. 4. Reduction of the feedback inherent in intracellular Ca2+ release caused saltatoric Ca2+ waves, revealing the two principal steps underlying wave propagation: diffusion and regeneration. Threshold stimulation evoked abortive Ca2+ waves, caused by the limited recruitment of Ca2+ puffs. 5. The hierarchy of Ca2+ signalling events, from fundamental levels (blips) to intermediate levels (puffs) to Ca2+ waves, is a prototype for Ca2+ signal transduction for non-excitable cells, and is also analogous to the Ca2+ quarks, Ca2+ sparks and Ca2+ waves in cardiac muscle cells.
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Bootman et al. (1997) studied this question. Histamine application was evaluated on Subcellular Ca2+ release signals. Histamine application in HeLa cells evoked a hierarchy of Ca2+ signaling events, from fundamental blips to intermediate puffs to global Ca2+ waves, analogous to signaling in cardiac muscle cells.
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