title: Reduction of calcium release site models via moment fitting of phase-type distributions.
abstract: Models of calcium (Ca(2 +)) release sites derived from continuous-time Markov chain (CTMC) models of intracellular Ca(2 +) channels exhibit collective gating reminiscent of the experimentally observed phenomenon of Ca(2 +) puffs and sparks. In order to overcome the state-space explosion that occurs in compositionally defined Ca(2 +) 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 Ca(2 +). Although inspired by existing techniques for fitting moments of phase-type distributions, the automated reduction method for compositional Ca(2 +) release site models is unique in several respects and novel in this biophysical context.
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, VA 23187, USA. mdlama@wm.edu
authors.forename: M Drew
authors.initials: MD
authors.lastname: LaMar
authors.forename: Peter
authors.initials: P
authors.lastname: Kemper
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Smith
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D006801:Humans; D015640:Ion Channel Gating; D008390:Markov Chains; D008954:Models, Biological
chemical_list: D015220:Calcium Channels; D002118:Calcium