Altered voltage dependence of fractional Ca2+ current in N-methyl-D-aspartate channel pore mutants with a decreased Ca2+ permeability

Biophysical Journal
R Schneggenburger

Abstract

The Ca2+ permeability properties of an N-methyl-D-aspartate (NMDA) channel pore mutant (NR1E603K-NR2A) were studied using whole-cell patch-clamp recordings in human embryonic kidney cells. Measurements of reversal potential shifts indicated that the relative permeability of Ca2+ over monovalent ions, P(Ca)/P(M), was 1.6, a value reduced by a factor of approximately 2 with respect to the wild-type channel. The ratio of Ca2+ current over total current (fractional Ca2+ current), however, was 19.7 +/- 1% at -50 mV and 2 mM external Ca2+ concentration, a value similar to that of the wild-type channel, but 2.3-fold larger than that predicted by simple permeation models for the corresponding P(Ca)/P(M) value. The deviation from predicted values gradually disappeared with membrane depolarization. Similar results were obtained for two cysteine mutations at asparagine residues of the NR1 and NR2A subunits. When interpreted in terms of a two-barrier one-site model for ion permeation, the results indicate that changes in the relative Ca2+ permeability occur close to an internal energy barrier limiting ion permeation.

References

Nov 7, 1991·Nature·K MoriyoshiS Nakanishi
Jul 6, 1973·Biochimica Et Biophysica Acta·P Läuger
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Feb 1, 1994·The Journal of General Physiology·M M Zarei, J A Dani
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C E Jahr, C F Stevens
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J KupperJ Neyton
Jan 1, 1997·Neuron·R Schneggenburger, P Ascher

❮ Previous
Next ❯

Citations

Jul 27, 2007·Cell Biochemistry and Biophysics·Toshihiro TakataShan Ping Yu
Sep 10, 2003·Progress in Neurobiology·Shan Ping Yu
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Jun 4, 1999·Biophysical Journal·R C AranedaM V Bennett
Feb 21, 2002·Molecular Pharmacology·Bryce VisselGary L Westbrook
Jul 25, 2018·The Journal of General Physiology·Kasper B HansenStephen F Traynelis
Jan 6, 2015·The Journal of Physiology·James E Huettner

❮ 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.