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Quantitative Analysis of a Fully Generalized Four-State Kinetic Scheme

Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland 21201

Correspondence: Address reprint requests to L. Goldman, Tel.: 410-706-5713; E-mail: lgoldman{at}som.umaryland.edu.

To describe the macroscopic behavior of many ion channels, at a minimum a four-state kinetic scheme is needed to provide for three processes: a delay in activation development, the activation process, and inactivation. I present here an analytical solution for a fully generalized four-state kinetic scheme in which every state can transit to every other state and any initial conditions can be specified. The solution describes the time courses of the probabilities of occupancy of each state during a step change in the rate constants of the scheme and includes closed-form expressions for the relaxation time constants and steady-state probabilities of occupancy as functions of the rate constants. Solutions for several relevant special cases are also included along with demonstrations that the general solution yields the correct behavior for several reduced or special cases where the result is independently known.