Abstract
Local intracellular calcium (C a2+) signals arise due to the release of C a2+ ions from internal stores into the cytosol through small clusters of inositol-1,4,5-triphosphate (I P3 ) receptors. To explain single I P3 receptor open probability data from nuclear patch clamp experiments, theoretical simulations have favored the existence of an agonist-independent conformational transition(AICT) from closed to an open state. We present results from a computational study wherein we explore the impact of the proposed agonist independent conformational transition on the collective release of calcium from I P3 R clusters. A wealth of experimental data profiles collective cluster release. Our results show that consistency of cluster release between theory and experiments in fact constrains the kinetics of the agonist-independent conformational transition (AITC) to values which lead to small open probabilities for a single I P3 receptor, inconsistent with nuclear patch clamp experimental data.
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