60 Accounting for stochastic gating whilst estimating ion channel kinetics from whole-cell voltage-clamp data

Oregon Convention Center 

The heartbeat is coordinated by ion-channels in cell membranes that change their conformation, a process known as gating, allowing ions to pass through them. Mathematical models of cardiac ion channels can be defined as biochemical reactions describing the transitions between the ion channel configurations. Whole-cell voltage-clamp data allows us to calibrate the parameters of such mathematical models. However, standard approaches do not distinguish between stochastic noise and measurement errors, and the resulting estimates can be biased. To overcome these limitations, we propose a state-space model including a set of Itô-type stochastic differential equations describing ion channel gating, coupled with an Ohmic equation linking the noisy measurements to the ion channel configurations. We developed an inference procedure to estimate the unknown parameters, based on maximum likelihood. Synthetic studies show that our proposed method can infer the unknown parameters with low uncertainty. These results will improve models of ion channel dynamics by accounting for stochastic gating and measurement errors during fitting.

State-space models

expectation-maximization

parameter inference

ion channels

cardiac electrophysiology

uncertainty quantification 

Uncertainty Quantification in Complex Systems Interest Group