The activity of ion channel proteins is central to many physiological processes, including synaptic transmission and impulse propagation in the nervous system, the control of cardiac function and vascular resistance, salt and water transport in epithelia, and the control of hormone secretion Central to the understanding of ion channel function is the characterization of the stochastic behavior of single channels as recorded using the patch clamp technique. Based on this kinetic characterization, molecular details such as ligand binding rates and the rates and patterns of conformational changes can be elucidated. Recently, hidden Markov models have been investigated for application to kinetic characterization of ion channels. We will advance this work by creating and evaluating a computer program to analyze single-channel data and characterize ion channel kinetics using hidden Markov models. The application of this analysis promises to allow meaningful kinetic information to be obtained from channels having low conductances (e.g. CFTR and Ca++ channels) or rapid kinetics (synaptic receptors, Na+ channels) whose characterization has been hindered in the past by poor signal-to-noise ratio in the recordings. Computer programs providing hidden Markov analysis of patch-clamp recordings will be viable commercial products.National Institute of General Medical Sciences (NIGMS)
