help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Biophys. J. BioFAST: First Published October 19, 2007. doi:10.1529/biophysj.107.116798
© 2007 by the Biophysical Society.

A more recent version of this article appeared on February 15, 2008.
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Supplement
Right arrow All Versions of this Article:
biophysj.107.116798v1
94/4/1169    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gillespie, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gillespie, D.

BIOPHYSICAL THEORY AND MODELING

Energetics of divalent selectivity in a calcium channel: the ryanodine receptor case study

Dirk Gillespie 1*

1 Rush University Medical Center

* To whom correspondence should be addressed. E-mail: dirk_gillespie{at}rush.edu.

Submitted on July 6, 2007
Revised on August 11, 2007
Accepted on 18 September 2007


  Abstract
A model of the ryanodine receptor (RyR) calcium channel is used to study the energetics of binding selectivity of Ca2+ vs. monovalent cations. RyR is a calcium-selective channel with a DDDD locus in the selectivity filter, similar to the EEEE locus of the L-type calcium channel. While the affinity of RyR for Ca2+ is in the millimolar range (as opposed to the micromolar range of the L-type channel), the ease of single-channel measurements compared to L-type and its similar selectivity filter make RyR an excellent candidate for studying calcium selectivity. A Poisson-Nernst-Planck/Density Functional Theory model of RyR is used to calculate the energetics of selectivity. Ca2+ vs. monovalent selectivity is driven by the charge/space competition mechanism in which selectivity arises from a balance of electrostatics and the excluded volume of ions in the crowded selectivity filter. While electrostatic terms dominate the selectivity, the much smaller excluded-volume term also plays a substantial role. In the D4899N and D4938N mutations of RyR that are analyzed, substantial changes in specific components of the chemical potential profiles are found far from the mutation site. These changes result in the significant reduction of Ca2+ selectivity found in both theory and experiments.

Key Words: Poisson-Nernst-Planck, calcium channels, density functional theory, ryanodine receptor, selectivity




This article has been cited by other articles:


Home page
 Biophys. JHome page
D. Gillespie and M. Fill
Intracellular Calcium Release Channels Mediate Their Own Countercurrent: The Ryanodine Receptor Case Study
Biophys. J., October 15, 2008; 95(8): 3706 - 3714.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
D. Gillespie and D. Boda
The Anomalous Mole Fraction Effect in Calcium Channels: A Measure of Preferential Selectivity
Biophys. J., September 15, 2008; 95(6): 2658 - 2672.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
D. Gillespie, D. Boda, Y. He, P. Apel, and Z. S. Siwy
Synthetic Nanopores as a Test Case for Ion Channel Theories: The Anomalous Mole Fraction Effect without Single Filing
Biophys. J., July 15, 2008; 95(2): 609 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
D. Boda, W. Nonner, D. Henderson, B. Eisenberg, and D. Gillespie
Volume Exclusion in Calcium Selective Channels
Biophys. J., May 1, 2008; 94(9): 3486 - 3496.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by the Biophysical Society.