Submicroscopic calcium signals as fundamental events of excitation‐‐contraction coupling in guinea‐pig cardiac myocytes.

1. Subcellularly localized Ca2+ signals have been proposed to represent elementary events of cardiac Ca2+ signalling (Ca2+ sparks), whereby an individual sarcolemmal L‐type Ca2+ channel locally controls opening of a single (or a few) Ca2+ release channels in the sarcoplasmic reticulum (SR). 2. To investigate directly the elementary nature of this Ca(2+)‐induced Ca2+ release mechanism we used flash photolysis of caged Ca2+ while simultaneously measuring the intracellular Ca2+ concentration ([Ca2+]i) with a laser‐scanning confocal microscope. 3. Power spectral analysis of the confocal images performed in the spatial domain revealed that only Ca2+ signalling events involving the L‐type Ca2+ channel pathway gave rise to Ca2+ sparks. In contrast, SR Ca2+ release triggered by photolytic [Ca2+]i jumps resulted in Ca2+ transients that were always spatially homogeneous. 4. From these findings we conclude that the fundamental event of Ca2+ signalling in cardiac muscle may be smaller in size or amplitude than a Ca2+ spark. 5. We term this event a ‘Ca2+ quark’ possibly resulting from gating of a single SR Ca2+ release channel. It is proposed that concerted activation of several ‘Ca2+ quarks’ may be required for a Ca2+ spark. The ‘Ca2+ quark’ could also be the fundamental event in other cell types implementing a hierarchical Ca2+ signalling concept.