An analytical tool for elucidating ion-channel molecular mechanisms from macroscopic current traces
© Fribourg et al; licensee BioMed Central Ltd. 2010
Published: 20 July 2010
Building models to describe the dynamics of macroscopic currents through ion channels has been the object of numerous studies in the literature with the aim of understanding ion-channel function. Following a perturbation, typically a step in voltage or ligand concentration, the response is formed by a combination of different processes such as activation or inactivation that pull the measured quantity (macroscopic current) in the same or opposite directions with different strengths and different time constants. Although this dynamic response can be readily recorded in time, the relationship between the underlying processes cannot be easily teased apart without structural analysis or single-channel recordings. An example is the classic problem of determining from sodium-channel macroscopic traces whether the activation and inactivation processes occur in parallel or inactivation is dependent on previous activation.
We show that we can apply this methodology to voltage-activated L-type calcium-channel traces from voltage-clamp experiments and derive a molecular kinetic scheme. Furthermore, we show how these molecular kinetic schemes can reveal the mechanism of action of drugs that act on calcium-channels. Our results explain the utility of this methodology for obtaining information on molecular mechanisms from electrophysiological traces. Moreover, they illustrate how the analysis could be generalized to recordings from other biological experiments.
This article is published under license to BioMed Central Ltd.