Stochastic models of ion channels
Publication Date
July 5, 2001
Creator
Abstract
This thesis is concerned with models and inference for single ion channels.
Molecular modelling studies are used as the basis for biologically realistic, large state-space gating models of the nicotinic acetylcholine receptor which enable single-channel kinetic behaviour to be characterized in terms of a small number of free parameters. A model is formulated which incorporates known structural information concerning pentameric subunit composition, interactions between neighbouring subunits and knowledge of the behaviour of agonist binding sites within the receptor-channel proteins. Expressions are derived for various channel properties and results are illustrated using numerical examples. The model is adapted and extended to demonstrate how properties of the calcium ion-activated potassium ion channel may be modelled.
A two-state stochastic model for ion channels which incorporates time interval omission is examined. Two new methods for overcoming a non-identifiability problem induced by time interval omission are introduced and simulation studies are presented in support of these methods. A framework is presented for analysing the asymptotic behaviour of the method-of-moments estimators of the mean lengths of open and closed sojourns. This framework is used to clarify the origin of the non-identifiability and to construct confidence sets for the mean sojourn lengths. A conjecture concerning the number of solutions of the moment estimating equations is proved.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Mathematical Sciences (UK)
eprints ID
11277
UoN Repository URI
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