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How Does Intracellular Ca²⁺ Oscillate: By Chance or by the Clock?

Alexander Skupin ^*, Helmut Kettenmann , Ulrike Winkler , Maria Wartenberg , Heinrich Sauer ^¶, Stephen C. Tovey , Colin W. Taylor  and Martin Falcke ^*

^* Department of Theoretical Physics, Hahn Meitner Institut, Berlin, Germany; Department of Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany; FZ Lobeda Kardiologie, Universitätsklinikum Jena, Jena, Germany; ^¶ Physiologisches Institut, Justus-Liebig-Universität, Giessen, Germany; and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom

Correspondence: Address reprint requests to Martin Falcke, Tel.: 49-30-80-62-26-27; E-mail: falcke{at}hmi.de.

Ca²⁺ oscillations have been considered to obey deterministic dynamics for almost two decades. We show for four cell types that Ca²⁺ oscillations are instead a sequence of random spikes. The standard deviation of the interspike intervals (ISIs) of individual spike trains is similar to the average ISI; it increases approximately linearly with the average ISI; and consecutive ISIs are uncorrelated. Decreasing the effective diffusion coefficient of free Ca²⁺ using Ca²⁺ buffers increases the average ISI and the standard deviation in agreement with the idea that individual spikes are caused by random wave nucleation. Array-enhanced coherence resonance leads to regular Ca²⁺ oscillations with small standard deviation of ISIs.