Abstract
Models of calcium (Ca2 +) release sites derived from continuous-time Markov chain (CTMC) models of intracellular Ca2 + channels exhibit collective gating reminiscent of the experimentally observed phenomenon of Ca2 + puffs and sparks. In order to overcome the state-space explosion that occurs in compositionally defined Ca2 + release site models, we have implemented an automated procedure for model reduction that replaces aggregated states of the full release site model with much simpler CTMCs that have similar within-group phase-type sojourn times and inter-group transitions. Error analysis based on comparison of full and reduced models validates the method when applied to release site models composed of 20 three-state channels that are both activated and inactivated by Ca2 +. Although inspired by existing techniques for fitting moments of phase-type distributions, the automated reduction method for compositional Ca2 + release site models is unique in several respects and novel in this biophysical context.
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