Journal article
Estimating the voltage-dependent free energy change of ion channels using the median voltage for activation
The Journal of general physiology, Vol.139(1), pp.3-17
01/01/2012
DOI: 10.1085/jgp.201110722
PMCID: PMC3250103
PMID: 22155736
Abstract
Voltage-gated ion channels are crucial for electrical activity and chemical signaling in a variety of cell types. Structure-activity studies involving electrophysiological characterization of mutants are widely used and allow us to quickly realize the energetic effects of a mutation by measuring macroscopic currents and fitting the observed voltage dependence of conductance to a Boltzmann equation. However, such an approach is somewhat limiting, principally because of the inherent assumption that the channel activation is a two-state process. In this analysis, we show that the area delineated by the gating charge displacement curve and its ordinate axis is related to the free energy of activation of a voltage-gated ion channel. We derive a parameter, the median voltage of charge transfer (V(m)), which is proportional to this area, and prove that the chemical component of free energy change of a system can be obtained from the knowledge of V(m) and the maximum number of charges transferred. Our method is not constrained by the number or connectivity of intermediate states and is applicable to instances in which the observed responses show a multiphasic behavior. We consider various models of ion channel gating with voltage-dependent steps, latent charge movement, inactivation, etc. and discuss the applicability of this approach in each case. Notably, our method estimates a net free energy change of approximately -14 kcal/mol associated with the full-scale activation of the Shaker potassium channel, in contrast to -2 to -3 kcal/mol estimated from a single Boltzmann fit. Our estimate of the net free energy change in the system is consistent with those derived from detailed kinetic models (Zagotta et al. 1994. J. Gen. Physiol. doi:10.1085/jgp.103.2.321). The median voltage method can reliably quantify the magnitude of free energy change associated with activation of a voltage-dependent system from macroscopic equilibrium measurements. This will be particularly useful in scanning mutagenesis experiments.
Details
- Title: Subtitle
- Estimating the voltage-dependent free energy change of ion channels using the median voltage for activation
- Creators
- Sandipan Chowdhury - University of Wisconsin–MadisonBaron Chanda - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- The Journal of general physiology, Vol.139(1), pp.3-17
- DOI
- 10.1085/jgp.201110722
- PMID
- 22155736
- PMCID
- PMC3250103
- NLM abbreviation
- J Gen Physiol
- ISSN
- 0022-1295
- eISSN
- 1540-7748
- Publisher
- Rockefeller Univ Press
- Number of pages
- 15
- Grant note
- Shaw Scientist Award R01GM084140 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM084140 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2012
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984297503002771
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