PMID: 9450938Mar 7, 1998Paper

Ion channel selectivity through stepwise changes in binding affinity

The Journal of General Physiology
T X Dang, Edwin W McCleskey

Abstract

Voltage-gated Ca2+ channels select Ca2+ over competing, more abundant ions by means of a high affinity binding site in the pore. The maximum off rate from this site is approximately 1,000x slower than observed Ca2+ current. Various theories that explain how high Ca2+ current can pass through such a sticky pore all assume that flux occurs from a condition in which the pore's affinity for Ca2+ transiently decreases because of ion interactions. Here, we use rate theory calculations to demonstrate a different mechanism that requires no transient changes in affinity to quantitatively reproduce observed Ca2+ channel behavior. The model pore has a single high affinity Ca2+ binding site flanked by a low affinity site on either side; ions permeate in single file without repulsive interactions. The low affinity sites provide steps of potential energy that speed the exit of a Ca2+ ion off the selectivity site, just as potential energy steps accelerate other chemical reactions. The steps could be provided by weak binding in the nonselective vestibules that appear to be a general feature of ion channels, by specific protein structures in a long pore, or by stepwise rehydration of a permeating ion. The previous ion-interaction models and thi...Continue Reading

References

Oct 1, 1978·The Journal of General Physiology·B Hille, W Schwarz
Jan 1, 1991·Annals of the New York Academy of Sciences·C M Armstrong, J Neyton
Sep 1, 1990·The Journal of General Physiology·N YamashitaS Hagiwara
Jan 1, 1987·Annual Review of Biophysics and Biophysical Chemistry·T Begenisich
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D D Friel, R W Tsien
Jun 1, 1973·The Journal of General Physiology·A M Woodhull
Nov 1, 1972·The Journal of General Physiology·F Bezanilla, C M Armstrong
Feb 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·B Hille
Sep 1, 1984·The Journal of Physiology·K S Lee, R W Tsien
Oct 1, 1982·The Journal of Physiology·E M FenwickE Neher
May 6, 1984·Nature·P Hess, R W Tsien
Aug 1, 1994·Quarterly Reviews of Biophysics·J J FalkeO B Peersen
Apr 1, 1996·The Journal of General Physiology·C Miller
Jun 1, 1997·The Journal of General Physiology·L Polo-Parada, S J Korn

❮ Previous
Next ❯

Citations

Aug 23, 2001·Archives of Biochemistry and Biophysics·B S ZhorovV S Ananthanarayanan
Jun 17, 2011·European Biophysics Journal : EBJ·María Del Rocío Cantero, Horacio F Cantiello
Mar 7, 1998·The Journal of General Physiology·H A Lester, D A Dougherty
Oct 6, 1998·The Journal of General Physiology·P StampeT Begenisich
Jun 3, 1999·The Journal of General Physiology·E W McCleskey
Jun 3, 1999·The Journal of General Physiology·W NonnerB Eisenberg
Jun 3, 1999·The Journal of General Physiology·D G Levitt
Sep 27, 2000·The Journal of General Physiology·R K ClouesW A Sather
May 2, 2001·The Journal of General Physiology·J Thompson, T Begenisich
Dec 2, 2004·The Journal of General Physiology·Emilio Carbone
May 31, 2007·The Journal of General Physiology·Olga BabichRoman Shirokov
Sep 26, 2007·The Journal of General Physiology·Thierry CensPierre Charnet
May 31, 2007·The Journal of General Physiology·Riccardo Olcese
Apr 29, 2009·The Journal of General Physiology·Dezso BodaWolfgang Nonner
Jan 7, 1999·The EMBO Journal·C DzejaS Frings
Dec 10, 2002·Annual Review of Physiology·William A Sather, Edwin W McCleskey
Feb 8, 2006·Annual Review of Physiology·Grzegorz OwsianikBernd Nilius
Jan 23, 2014·Pflügers Archiv : European journal of physiology·Yaroslav M Shuba
Feb 26, 2014·The Journal of General Physiology·Megumi Yamashita, Murali Prakriya
Aug 13, 2014·The Journal of General Physiology·Zafir BuraeiKeith S Elmslie
Jul 27, 1999·The Journal of Physiology·J WarnatA Cavalié
Aug 10, 2015·Trends in Biochemical Sciences·William A Catterall, Ning Zheng
Mar 31, 2015·Progress in Neurobiology·Felix NeumaierToni Schneider
Dec 7, 2000·Biophysical Journal·J R SerranoS W Jones
Feb 13, 2001·Biophysical Journal·B CorryS H Chung
Feb 13, 2001·Biophysical Journal·N Ilan, S A Goldstein
Mar 24, 2015·PloS One·Elisa CarrilloFroylan Gomez-Lagunas

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.