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Release Currents of IP₃ Receptor Channel Clusters and Concentration Profiles

Hahn Meitner Institut, 14109 Berlin, Germany

Correspondence: Address reprint requests to M. Falcke, E-mail: falcke{at}hmi.de.

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 µm 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.

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