Ion channels play key roles in a many physiological processes such as the integration of information in neurones, propagation of action potentials, synaptic transmission. The gating of ion channels can be described by reaction mechanisms with discrete kinetic states. Whereas it is the properties of the kinetic states that are needed to describe gating, the information obtained from the analysis of single channel currents gives open and closed dwell-time distributions, which are described by sums of exponential components. In theory, the number of components will equal the number of open and closed kinetic states (i.e. a model with four kinetic open states will produce an open interval dwell time distribution described by the sum of four exponential components). However, not all of the kinetic states may be detected. Furthermore, the relationship between the dwell-time distributions and the kinetic states is complex because all of the rate constants in the model can contribute to each component in the dwell-time distributions (Colquhoun & Hawkes, 1982). The purpose of this study is to relate kinetic states to exponential components. Using simulations of Markov gating mechanisms, we investigate the relationships between the exponential components and the kinetic states. The linkage between components and states is defined in terms of the proportion of time a given kinetic state contributes to each exponential component, and thus ranges from 0, (no linkage) to 1, (complete linkage), and also as the mean number of sojourns to each kinetic state for each interval in a given exponential component. For the model in Fig. 1, the calculated time linkages between the lifetime of closed state 1 and the fast and slow time constants was 0.91 and 0.66, respectively. The time linkage between closed state 2 and the fast and slow closed components was 0.093 and 0.34, respectively. The inclusion of missed events (0.2 ms dead time) reduced the linkage of closed state 1 to ~0.6 for both the fast and slow components, but had little effect on the linkage between closed state 3 and the two components. Under certain conditions, the time constants of the specified components obtained from dwell time distributions can be approximated by the lifetimes of certain states, and for other conditions there is much less linkage. For model 1 it was found that to obtain a time linkage of 0.95 between the lifetime of shut state 2 and the slowest shut time component, the lifetime of shut state 2 had to be at least 33-fold greater than the lifetime of shut state 2. In addition, it is shown graphically why the time constant of a component can be considerably faster than the mean lifetime of any of the states in the model. An understanding of the relationships between components and states will aid in the interpretation of single channel dwell-time distributions.
King's College London (2005) J Physiol 565P, C85
Communications: Revealing the linkage (contribution) of each kinetic state in the gating mechanisms for ion channels to the exponential components in the observed dwell-time distributions
Shelley, Chris ; Magleby, Karl L. ;
1. Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL, USA.
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Figure 1. Model used to examine linkages between state lifetimes and the time constants of the exponential components.
Where applicable, experiments conform with Society ethical requirements.