Spiral calcium waves: implications for signalling.

Spiral patterns of intracellular Ca2+ release demonstrate a direct relationship between increasing wavefront curvature and increasing propagation velocity. An equally important phenomenon is the annihilation of colliding Ca2+ waves, which reveals an underlying refractory period during which further Ca2+ release is temporarily inhibited. Treatment of intracellular Ca2+ release as an excitable medium accounts for both observations. This theoretical framework is analogous to the more familiar concept of electrical excitability in neuronal membranes. In this analogy, the inositol 1,4,5-trisphosphate receptor ion channel plays a role analogous to that of Na+ channels while Ca(2+)-induced Ca2+ release provides the mechanism for excitation. Furthermore, Ca(2+)-ATPases play a role similar to that of the K+ channels in neuronal excitation, that is, they return the system to rest. We demonstrated that overexpression of a sarco/endoplasmic reticulum Ca(2+)-ATPase increases the frequency of Ca2+ wave activity. More recent experiments reveal a strong dependence of the propagation velocity on wavelength as predicted by the dispersion relation of excitability. This important result accounts for an observed correlation between wave frequency and spatial dominance of Ca2+ foci and suggests a new mechanism for the encoding of signal information.