Research Report 2010 - MDC

Simulation of line-scan images of Ca 2+ release upon a step increase ofIP3 in Xenopus oocytes. Fluorescence increases with the cytosolic free[Ca 2+ ]. The color indicates low fluorescence with blue and high fluorescencewith red. The control simulation uses 40 µM fluorescent dye asthe only exogenous Ca 2+ buffer and the other panels additionally theindicated amount of slow EGTA or fast BAPTA. We see the typicalshortening of the fluorescence signal by competition between EGTAand the dye and the prolongation of release by BAPTA.regime. In the high density regime, buffers with slowbinding rates like EGTA and a K D in the order of magnitudeof cytosolic Ca 2+ resting levels shape the timecourse of fluorescence signals by buffer competition butdo not shape release at IP 3 R clusters. Buffers with fastbinding rates shape release by delaying Ca 2+ -dependentinhibition of IP 3 Rs. That causes larger spikes of the numberof open channels and prolongs release. The low densityregime comprises the effect on spike sequencesdescribed above and termination of repetitive spiking bydecoupling of clusters by large [EGTA] or [BAPTA].Our modeling of actin based cell motility aims at suggestingmechanisms which explain the velocitydynamics observed with bacterial propulsion, the morphodynamictypes of protrusions observed at the leadingedge of a variety of motile cells and to link the typesto the state of signaling pathways. The similarity of themolecular components involved in both groups ofprocesses suggests it to be possible to describe bothbacterial propulsion and the dynamics of protrusion bymodels which are distinguished essentially only byparameter values but consist otherwise of very similarequations. We were able to derive such a model from ahypothesis on the relevant processes and to demonstratethe existence of the observed dynamic regimeslike steady and oscillatory movement. The research ofthe group will now establish the link between cell signalingand morphodynamic types.We are also developing a model of cardiac myocytes. Itmodels individual L-type and ryanodine receptor channelswith stochastic state transitions and will still beable to simulate cellular dynamics because of the useof multiscale techniques. The goal of this modelingeffort is to simulate excitation contraction couplingwith realistic intracellular Ca 2+ and membrane potentialdynamics. The model will serve to investigate conditionsand dynamics of Ca 2+ alternans and membranepotential alternans in first studies. It will then beadapted and enhanced according to the needs ofexperimental research at the MDC.Selected PublicationsGin, E, Falcke, M, Wagner II, LE, Yule, DI, Sneyd, J. (2009). A Kinetic Modelof the Inositol Trisphosphate Receptor Based on Single-Channel Data.Biophys.J. 96, 4053-4062.Taufiq-Ur-Rahman, Skupin, A, Falcke, M, Taylor, CW. (2009). Clustering ofInsP3 receptors by InsP3 retunes their regulation by InsP3 and Ca 2+ .Nature 458, 655-659.Skupin, A, Kettenmann, H, Winkler, U, Wartenberg, M, Sauer, H, Tovey, S,Taylor, CW, Falcke, M. (2008). How does intracellular Ca 2+ oscillate: bychance or by the clock?. Biophys. J. 94, 2404-2411.Zeller, S, Rüdiger, S, Engel, H, Sneyd, J, Warnecke, G, Parker, I, Falcke, M.Modeling of the modulation by buffers of Ca2+ release through clustersof IP3 receptors. Biophys. J., in pressEnculescu, M, Gholami, A, Falcke, M. (2008). Dynamic regimes andbifurcations in a model of actin based motility. Physical Review E 78,031915Technology Platforms 221