References of "Kettenmann, Helmut"
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See detailCalcium signals driven by single channel noise.
Skupin, Alexander UL; Kettenmann, Helmut; Falcke, Martin

in PLoS computational biology (2010), 6(8),

Usually, the occurrence of random cell behavior is appointed to small copy numbers of molecules involved in the stochastic process. Recently, we demonstrated for a variety of cell types that intracellular ... [more ▼]

Usually, the occurrence of random cell behavior is appointed to small copy numbers of molecules involved in the stochastic process. Recently, we demonstrated for a variety of cell types that intracellular Ca2+ oscillations are sequences of random spikes despite the involvement of many molecules in spike generation. This randomness arises from the stochastic state transitions of individual Ca2+ release channels and does not average out due to the existence of steep concentration gradients. The system is hierarchical due to the structural levels channel--channel cluster--cell and a corresponding strength of coupling. Concentration gradients introduce microdomains which couple channels of a cluster strongly. But they couple clusters only weakly; too weak to establish deterministic behavior on cell level. Here, we present a multi-scale modelling concept for stochastic hierarchical systems. It simulates active molecules individually as Markov chains and their coupling by deterministic diffusion. Thus, we are able to follow the consequences of random single molecule state changes up to the signal on cell level. To demonstrate the potential of the method, we simulate a variety of experiments. Comparisons of simulated and experimental data of spontaneous oscillations in astrocytes emphasize the role of spatial concentration gradients in Ca2+ signalling. Analysis of extensive simulations indicates that frequency encoding described by the relation between average and standard deviation of interspike intervals is surprisingly robust. This robustness is a property of the random spiking mechanism and not a result of control. [less ▲]

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See detailHow does intracellular Ca2+ oscillate: by chance or by the clock?
Skupin, Alexander UL; Kettenmann, Helmut; Winkler, Ulrike et al

in Biophysical journal (2008), 94(6), 2404-11

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 ... [more ▼]

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. [less ▲]

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See detailTemperature and nitric oxide control spontaneous calcium transients in astrocytes.
Schipke, Carola G.; Heidemann, Antje; Skupin, Alexander UL et al

in Cell calcium (2008), 43(3), 285-95

Transient spontaneous increases in the intracellular Ca2+ concentration have been frequently observed in astrocytes in cell culture and in acutely isolated slices from several brain regions. Recent in ... [more ▼]

Transient spontaneous increases in the intracellular Ca2+ concentration have been frequently observed in astrocytes in cell culture and in acutely isolated slices from several brain regions. Recent in vivo experiments, however, reported only a low frequency of spontaneous Ca2+ events in astrocytes. Since the ex vivo experiments were usually performed at temperatures lower than physiological body temperature, we addressed the question whether temperature could influence the spontaneous Ca2+ activity in astrocytes. Indeed, comparing the frequency and spike width of spontaneous Ca2+ transients in astrocytes at temperatures between 20 and 37 degrees C in culture as well as in acute cortical slices from mouse brain, revealed that spontaneous Ca2+ responses occurred frequently at low temperature and became less frequent at higher temperature. Moreover, the single Ca2+ events had a longer duration at low temperature. We found that nitric oxide (NO) mimicked the increase in spontaneous Ca2+ activity and that an NO-synthase inhibitor attenuated the effect of lowering the temperature. Thus, temperature and NO are major determinants of spontaneous astrocytic Ca2+ signalling. [less ▲]

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