PMID: 8967988Dec 1, 1996Paper

The role of inactivation in open-channel block of the sodium channel: studies with inactivation-deficient mutant channels

Molecular Pharmacology
A O GrantJ R Moorman

Abstract

Inactivation has been implicated as an important determinant of the block of Na+ channel by local anesthetic-class drugs. This proposition has been difficult to examine because agents used to modify inactivation change other channel properties and both inactivated and blocked channels do not conduct. We used site-directed mutagenesis of Phe1304 to glutamine in the linker between the third and fourth domains of the mu-1 Na+ channel to slow inactivation. Wild-type and mutant channels were expressed in frog oocytes. Macropatch and single-channel currents were recorded in cell-attached membrane patches. The F1304Q mutation increased mean open time (1.7 fold at -20 mV) and reduced the probability that the channel would fail to open. Closed times were best fit by a double-exponential function, suggesting that the inactivated state transitions were no longer absorbing. In wild-type channels, 100 microM disopyramide decreased mean open time from 1.64 +/- 0.08 to 0.34 +/- 0.04 msec. Total open time per trial was decreased 2-fold. There also was a marked increase in the fraction of null sweeps. In the inactivation-deficient mutant channel, mean and total open times were also reduced. These data indicate that even when inactivation is slo...Continue Reading

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.