Release currents of IP₃ receptor channel clusters and concentration profiles

We simulate currents and concentration profiles generated by Ca2+ release from the endoplasmic reticulum (ER) to the cytosol through IP3 receptor channel clusters. Clusters are described as conducting pores in the lumenal membrane with a diameter from 6 nm to 36 nm. The endoplasmic reticulum is modeled as a disc with a radius of 1–12 mm and an inner height of 28 nm. We adapt the dependence of the currents on the trans Ca2+ concentration (intralumenal) measured in lipid bilayer experiments to the cellular geometry. Simulated currents are compared with signal mass measurements in Xenopus oocytes. We find that release currents depend linearly on the concentration of free Ca2+ in the lumen. The release current is approximately proportional to the square root of the number of open channels in a cluster. Cytosolic concentrations at the location of the cluster range from 25 μM to 170 μM. Concentration increase due to puffs in a distance of a few micrometers from the puff site is found to be in the nanomolar range. Release currents decay biexponentially with timescales of < 1 s and a few seconds. Concentration profiles decay with timescales of 0.125–0.250 s upon termination of release.

Reactive clusters on a membrane

We investigate the reaction dynamics of diffusive molecules with immobile binding partners. The fixed reactants build clusters that comprise just a few tens of molecules, which leads to small cluster sizes. These molecules participate in the reaction only if they are activated. The dynamics of activation is mapped to a time-dependent size of an active region within the cluster. We focus on the deterministic description of the dynamics of a single cluster. The spatial setup accounts for one of the most important determinants of the dynamics of a cluster, i.e. diffusional transport of reaction partners toward or away from the active region of the cluster. We provide numerical and analytical evidence that diffusion influences decisively the dynamic regimes of the reactions. The application of our methods to intracellular Ca²⁺ dynamics shows that large local concentrations saturate the Ca²⁺ feedback to the channel state control. That eliminates oscillations depending on this feedback.