PMID: 9002421Jan 1, 1997Paper

Cysteine mapping in the ion selectivity and toxin binding region of the cardiac Na+ channel pore

The Journal of Membrane Biology
S ChenG E Kirsch

Abstract

Aqueous exposure of critical residues in the selectivity region of voltage gated Na+ channels was studied by cysteine-scanning mutagenesis at three positions in each of the SS2 segments of domains III (D3) and IV (D4) of the human heart Na+ channel. Ionic currents were modified by charged cysteine-specific methanethiosulfonate (MTS) reagents, (2-aminoethyl)methanethiosulfonate (MTSEA+) and (2-sulfonatoethyl)methanethiosulfonate (MTSES-) in all six of the Cys-substituted channels, including Trp --> Cys substitutions at homologous positions in D3 and D4 that were predicted in secondary structure models to have buried side chains. Furthermore, in the absence of MTS modification, each of the Cys mutants showed a reduction in tetrodotoxin (TTX) block by a factor >10(2). Cysteine substitution without MTS modification abolished the alkali metal ion selectivity in K1418C (D3), but not in A1720C (the corresponding position in D4) suggesting that the lysine but not the alanine side chains contribute to selectivity even though both were exposed. Neither position responded to MTSES- suggesting that these residues occupy either a size- or charge-restricted region of the pore. By contrast, MTSES- markedly increased, and MTSEA+ markedly decre...Continue Reading

Citations

Mar 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Chris R FeldmanMichael E Pfrender
Nov 21, 2009·The Journal of Biological Chemistry·James J MatsudaFred S Lamb
Feb 2, 1999·The Journal of General Physiology·C Townsend, R Horn
Nov 27, 2002·The Journal of General Physiology·Lixia YueDavid E Clapham
May 18, 2005·The Journal of General Physiology·Anita M Engh, Merritt Maduke
Jun 5, 2010·Proceedings. Biological Sciences·Chris R FeldmanMichael E Pfrender
Apr 15, 2010·Marine Drugs·Harry A Fozzard, Gregory M Lipkind
Nov 22, 2005·Biophysical Journal·Maarten VrouenraetsHenk Miedema
Jun 5, 2007·Biophysical Journal·Vincent P SantarelliRichard Horn

❮ 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.