Waiting time distributions for clusters of receptors

Abstract

Inositol 1,4,5-trisphosphate (IP(3)R) receptor channels control release of Ca(2+) from the endoplasmic reticulum into the cytosol of a cell. The binding of both 1,4,5-trisphosphate (IP(3)) and activating Ca(2+) is required for the channel to open. At high Ca(2+) concentrations, IP(3)Rs are inhibited. IP(3)Rs are composed of four identical subunits and form in clusters. Many models have been proposed to describe how the binding of IP(3) and Ca(2+) to subunits results in the opening and closing of IP(3)Rs. Here we compare the opening and closing probability distributions for clusters of IP(3)Rs, resulting from three different models. The distributions are calculated both analytically, using a method we have developed, and with simulations. We found significant differences in the behavior of the three models as the Ca(2+) and IP(3) concentrations are varied.

Derivation of Ca 2+ signals from puff properties reveals that pathway function is robust against cell variability but sensitive for control

“…That provides for the spatial coupling. We compute the opening probability distribution ψ o ðc;t − τÞ from the De Young-Keizer model, which is one of the standard models in the field (42,43) …”

Fundamental properties of Ca2+ signals

“…However, such a recovery timescale has not been observed with the local puff dynamics of IP 3 R clusters. Interpuff intervals (IPIs) exhibit a relative refractory period of a few seconds only [12,14,15,18,[33][34][35]. Hence, the negative feedback that determines the time scale of interspike intervals (ISIs) is different from the feedback contributing to IPI and requires global (whole cell) release events.…”

Calsequestrin mediates changes in spontaneous calcium release profiles

“…Quasi-equilibrium approximations based on separations of time-scales are used in obtaining the two-state CRU reduction. Recently, Higgins et al (2009) presented results which indicate that quasi-equilibrium assumptions introduces error into the statistics describing the activity of IP 3 receptors. However, their results indicate that the largest error for the expected closing time is obtained when the approximations are taken in the model in which sequential binding of IP 3 and Ca 2 + is assumed.…”