Towards a predictive model of Ca²⁺ puffs

We investigate key characteristics of Ca²⁺ puffs in deterministic and stochastic frameworks that all incorporate the cellular morphology of IP[subscript]3 receptor channel clusters. In a first step, we numerically study Ca²⁺ liberation in a three dimensional representation of a cluster environment with reaction-diffusion dynamics in both the cytosol and the lumen. These simulations reveal that Ca²⁺ concentrations at a releasing cluster range from 80 µM to 170 µM and equilibrate almost instantaneously on the time scale of the release duration. These highly elevated Ca²⁺ concentrations eliminate Ca²⁺ oscillations in a deterministic model of an IP[subscript]3R channel cluster at physiological parameter values as revealed by a linear stability analysis. The reason lies in the saturation of all feedback processes in the IP[subscript]3R gating dynamics, so that only fluctuations can restore experimentally observed Ca²⁺ oscillations. In this spirit, we derive master equations that allow us to analytically quantify the onset of Ca²⁺ puffs and hence the stochastic time scale of intracellular Ca²⁺ dynamics. Moving up the spatial scale, we suggest to formulate cellular dynamics in terms of waiting time distribution functions. This approach prevents the state space explosion that is typical for the description of cellular dynamics based on channel states and still contains information on molecular fluctuations. We illustrate this method by studying global Ca²⁺ oscillations.

Integrability for Relativistic Spin Networks

The evaluation of relativistic spin networks plays a fundamental role in the Barrett-Crane state sum model of Lorentzian quantum gravity in 4 dimensions. A relativistic spin network is a graph labelled by unitary irreducible representations of the Lorentz group appearing in the direct integral decomposition of the space of L^2 functions on three-dimensional hyperbolic space. To `evaluate' such a spin network we must do an integral; if this integral converges we say the spin network is `integrable'. Here we show that a large class of relativistic spin networks are integrable, including any whose underlying graph is the 4-simplex (the complete graph on 5 vertices). This proves a conjecture of Barrett and Crane, whose validity is required for the convergence of their state sum model.