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Disposition of Calcium Release Units in Agarose Gel for an Optimal Propagation of Ca²⁺ Signals

Manfred H. P. Wussling ^*, Ines Aurich ^*, Oliver Knauf ^*, Helmut Podhaisky  and Hans-Jürgen Holzhausen 

^* Julius Bernstein Institute of Physiology; Institute of Numerical Mathematics; and Institute of Pathology, Martin Luther University, Halle-Wittenberg, Germany

Correspondence: Address reprint requests to Professor Manfred H. P. Wussling, Martin Luther University, Julius Bernstein Institute of Physiology, Halle-Wittenberg, Magdeburger Strasse 6, D-06097 Halle/S, Germany. Tel.: 49-345-557-1392; E-mail: manfred.wussling{at}medizin.uni-halle.de.

Clusters of calcium-loaded sarcoplasmic reticulum (SR) vesicles in agarose gel were previously shown to behave as an excitable medium that propagates calcium waves. In a 3D-hexagonal disposition, the distance between neighboring spheres (which may stand for SR vesicles) is constant and the relationship between distance and vesicular protein concentration is expected to be nonlinear. To obtain a distribution of SR vesicles at different protein concentrations as homogeneous as possible, liquid agarose gels were carefully stirred. Electron micrographs, however, did not confirm the expected relationship between inter-SR vesicle distance and vesicular protein concentration. Light micrographs, to the contrary, resulted in a protein concentration-dependent disposition of clusters of SR vesicles, which is described by a linear function. Stable calcium waves in agarose gel occurred at SR vesicle protein concentrations between 7 and 16 g/l. At lower protein concentrations, local calcium oscillations or abortive waves were observed. The velocities of calcium waves were optimum at 12 g/l and amounted to nearly 60 µm/s. The corresponding distance of neighboring calcium release units was calculated to be 4 µm. The results further show that calcium signaling in the described reaction-diffusion system is optimal in a relatively small range of diffusion lengths. A change by ±2 µm resulted in a reduction of the propagation velocity by 40%. It would appear that 1), the distance between calcium release units (clusters of ryanodine receptors in cells) is a sensitive parameter concerning propagation of Ca²⁺ signals; and 2), a dysfunction of the reaction-diffusion system in living cells, however, might have a negative effect on the spreading of intracellular calcium signals, thus on the cell's function.