Nonlinear propagation of spherical calcium waves in rat cardiac myocytes

Abstract

Spontaneous calcium waves in enzymatically isolated rat cardiac myocytes were investigated by confocal laser scanning microscopy (CLSM) using the fluorescent Ca2+-indicator fluo-3 AM. As recently shown, a spreading wave of enhanced cytosolic calcium appears, most probably during Ca2+ overload, and is initiated by an elementary event called a "calcium spark." When measured by conventional fluorescence microscopy the propagation velocity of spontaneous calcium waves determined at several points along the cardiac myocyte was previously found to be constant. More precise measurements with a CLSM showed a nonlinear propagation. The wave velocity was low, close to the focus, and increased with increasing time and propagation length, approaching a maximum of 113 microns/s. This result was surprising, inasmuch as for geometrical reasons a decrease of the propagation velocity might be expected if the confocal plane is not identical with that plane where the focus of the wave was localized. It is suggested that the propagation velocity is essentially dependent on the curvature of the spreading wave. From the linear relationship of velocity versus curvature, a critical radius of 2.7 +/- 1.4 microns (mean +/- SD) was worked out, below which an outward propagation of the wave will not take place. Once released from a sufficiently extended cluster of sarcoplasmic reticulum release channels, calcium diffuses and will activate its neighbors. While traveling away, the volume into which calcium diffuses becomes effectively smaller than at low radii. This effect is the consequence of the summation of elementary events (Ca2+ sparks) and leads to a steeper increase of the cytosolic calcium concentration after a certain diffusion path length. Thus the time taken to reach a critical threshold of [Ca2+]i at the neighboring calcium release sites decreases with decreasing curvature and the wave will propagate faster.

Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

“…Therefore the ratio of transverse-to-longitudinal wave propagation velocity should be 7.9/0.8 to 17.1/1.8 (respectively) or 1.04, i.e., close to unity. This idea may explain the paradoxical observation that Ca 2ϩ waves are nearly spherical (21,22), despite the underlying Ca 2ϩ diffusion being asymmetric.…”

Signal sequence within FcγRIIA controls calcium wave propagation patterns: Apparent role in phagolysosome fusion

“…In the present study we have identified a specific sequence of three amino acids within the cytoplasmic region of Fc␥RIIA that controls the calcium wave pathway within living cells and, crucially, the ability of immune cells to destroy internalized targets via phagolysosome formation. Previous studies have identified calcium waves in certain cell types including oocytes, myocytes, and retinal pigment epithelial cell monolayers (23)(24)(25). To observe waves in smaller cells, we have developed methods to collect movies of traveling chemical waves in cells by using brief shutter speeds (17)(18)(19).…”

Dispersion Gap and Localized Spiral Waves in a Model for IntracellularCa2+Dynamics

“…The cytosol is the medium surrounded by the cell membrane, in which the cell organelles are embedded. Intracellular calcium waves were first observed in medaka eggs [4] and later on in Xenopus oocytes [5,6], hepatocytes [7], articular chondrocytes [8], and cardiac myocytes [9,10]. The local dynamics inside these cells is nonlinear release and uptake of Ca 21 from intracellular stores like the endoplasmatic reticulum (ER) and the mitochondria.…”