title: Precision of intracellular calcium spike timing in primary rat hepatocytes.
abstract: Extracellular stimuli are often encoded in the frequency, amplitude and duration of spikes in the intracellular concentration of calcium ([Ca2+]i). However, the timing of individual [Ca2+]i-spikes in relation to the dynamics of an extracellular stimulus is still an open question. To address this question, we use a systems biology approach combining experimental and theoretical methods. Using computer simulations, we predict that more naturalistic pulsed stimuli generate precisely-timed [Ca2+]i-spikes in contrast to the application of constant stimuli of the same dose. These computational results are confirmed experimentally in single primary rat hepatocytes upon alpha1-adrenergic stimulation. Hormonal signalling in analogy to neuronal signalling thus has the potential to make use of temporal coding on the level of single cells. The [Ca2+]i-signalling cascade provides a first example for increasing the information capacity of an intracellular regulatory signal beyond the known coding mechanisms of amplitude (AM) and frequency modulation (FM).
authors.affiliation: NRW Graduate School in Bioinformatics and Genome Research, Centre of Biotechnology, Bielefeld University, Germany. klaus.prank@cebitec.uni-bielefeld.de
authors.forename: K
authors.initials: K
authors.lastname: Prank
authors.forename: M
authors.initials: M
authors.lastname: Waring
authors.forename: U
authors.initials: U
authors.lastname: Ahlvers
authors.forename: A
authors.initials: A
authors.lastname: Bader
authors.forename: E
authors.initials: E
authors.lastname: Penner
authors.forename: M
authors.initials: M
authors.lastname: Möller
authors.forename: G
authors.initials: G
authors.lastname: Brabant
authors.forename: C
authors.initials: C
authors.lastname: Schöfl
mesh_terms: D000465:Algorithms; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D022781:Hepatocytes / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002118:Calcium