Revisiting IP3R channel clustering and calcium dynamics: From nano-waves to cellular oscillations - Spatio-temporal dynamics of intracellular calcium release

• Applicant: Privatdozent Dr. Sten Rüdiger
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Biophysics
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201188447

• Final Report Year: 2015

Final Report Abstract

The dynamics of Ca2+ is one of the most important signaling pathways in cells but their generation has only incompletely been understood so far. In our work within the DFG project we achieved important contributions to this problem. First, we proposed an explanation of the appearance of short-lived and long-lived calcium increases that can occur in the same cell at the same conditions. We proposed that this dichotomy is due to an underlying dynamics of inositol trisphosphate, which binds and unbinds on a long time-scale. Importantly, the binding state of IP3 can not be directly measured experimentally and thus theoretical work such as ours is crucial for the understanding of the calcium oscillations. However, our results on the dynamics of calcium itself can be compared to experimental measurements and provide indirect evidence for the proposed mechanism. Collaboration with an experimental group has indeed shown that the new model explains many aspects of Ca2+ oscillations including the different time scales of local and global signals and the refractoriness after global oscillations. Furthermore, the model also provides a new explanation of the concurrent increases in free [IP3 ] which are observed in some cell types. Our work on numerical characterization of Ca2+ gradients in cells has also been a valuable part of work on calcium dynamics in synapses. In the experimental part of this work it was determined that back-propagating electrical impulses serve to activate a Ca2+ channel inside the cell, thereby resulting in long-term changes in the calcium response in specific neuronal compartments. Using a detailed analysis of Ca2+ distribution in dendritic spines, we could estimate the distance of a Ca2+ controlled effector from the receptor channel, and thus characterize further this mechanism of synaptic plasticity, which may play an important role in memory formation.

Publications

• Diffusive spatio-temporal noise in a firstpassage time model for intracellular calcium release. The Journal of Chemical Physics, 138 (2013) 154103
  M.B. Flegg, S. Rüdiger, and R. Erban
  
• Frequency and Relative Prevalence of Calcium Blips and Puffs in a Model of Small IP3R Clusters. Biophysical Journal, 106 (2014), 2353-2363
  H. Qi, Y. Huang, S. Rüdiger, and J. Shuai
  
• Stochastic models of intracellular calcium signals, Physics Reports 534 (2014) 39-87
  S. Rüdiger
  
• Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model, PLOS Computational Biology 11 (2015), e1003965
  M. Rückl, I. Parker, J.S. Marchant, C. Nagaiah, F.W. Johenning, S. Rüdiger
  
• Ryanodine Receptor Activation induces Long-Term Plasticity of Spine Calcium Dynamics, PLOS Biology (2015)
  F.W. Johenning, A.K. Theis, U. Pannasch, M. Rückl, S. Rüdiger, D. Schmitz