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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.