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Fundamental calcium release events revealed by two‐photon excitation photolysis of caged calcium in guinea‐pig cardiac myocytes
Author(s) -
Lipp Peter,
Niggli Ernst
Publication year - 1998
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.1469-7793.1998.801bp.x
Subject(s) - ryanodine receptor , biophysics , calcium , endoplasmic reticulum , myocyte , chemistry , amplitude , coupling (piping) , gating , photodissociation , physics , biochemistry , optics , biology , photochemistry , materials science , microbiology and biotechnology , metallurgy , organic chemistry
1 In cardiac muscle, ‘Ca 2+ sparks’ have been proposed to underlie Ca 2+ ‐induced Ca 2+ release (CICR), and to result from openings of clusters of Ca 2+ channels (ryanodine receptors; RyRs) located in the sarcoplasmic reticulum membrane. 2 To investigate the elementary nature of these Ca 2+ signals directly, a diffraction‐limited point source of Ca 2+ was created in single cardiac myocytes by two‐photon excitation photolysis of caged Ca 2+ . Simultaneously, concentration profiles of released Ca 2+ were imaged at high temporal and spatial resolution with a laser‐scanning confocal microscope. 3 This approach enabled us to generate and detect photolytic Ca 2+ signals that closely resembled the Ca 2+ sparks occurring naturally, not only in amplitude and size, but also in their ability to trigger additional Ca 2+ sparks or Ca 2+ waves. 4 Surprisingly, at low photolytic power minuscule events with estimated Ca 2+ release fluxes 20‐40 times smaller than those calculated for a typical Ca 2+ spark were directly resolved. These events appeared to arise from the opening of a more limited number of RyRs (possibly one) or from RyRs exhibiting a different gating mode and may correspond to the elusive ‘Ca 2+ quark’. 5 The Ca 2+ quark represents the fundamental Ca 2+ release event of excitable cells implementing hierarchical Ca 2+ signalling systems with Ca 2+ release events of various but distinct amplitude levels (i.e. Ca 2+ quarks, Ca 2+ sparks and full cellular Ca 2+ transients). 6 A graded recruitment of nanoscopic Ca 2+ release domains (i.e. Ca 2+ quarks) exhibiting variable degrees of spatial coherence and coupling may then build up intermediate Ca 2+ signalling events (i.e. Ca 2+ sparks). This mechanism suggests the existence of Ca 2+ sparks caused by gating of a variable fraction of RyRs from within an individual cluster. Additional mobilization of a variable number of these Ca 2+ sparks enables cardiac cells to show graded cellular Ca 2+ transients. Similar recruitment processes may underlie regulation of Ca 2+ signalling on the cellular level in general.