Propofol inhibits prokaryotic voltage-gated Na+ channels by promoting activation-coupled inactivation

The Journal of General Physiology
Elaine YangManuel Covarrubias

Abstract

Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na+ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations (2-10 µM). In both Navs, propofol induced a hyperpolarizing shift of the pre-pulse inactivation curve without any significant effects on recovery from inactivation at strongly hyperpolarized voltages, demonstrating that propofol does not stabilize the inactivated state. Moreover, there was no evidence of fast or slow pore block by propofol in a non-inactivating NaChBac mutant (T220A). Propofol also induced hyperpolarizing shifts of the conductance-voltage relationships with negligible effects on the time constants of deactivation at hype...Continue Reading

References

Nov 1, 1977·The Journal of General Physiology·C M Armstrong, F Bezanilla
Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J W WestW A Catterall
Jul 1, 1973·The Journal of General Physiology·G R Strichartz
Nov 1, 1965·Anesthesiology·E I EgerB Brandstater
Jul 1, 1981·Physiological Reviews·C M Armstrong
May 1, 1983·The Journal of General Physiology·B P BeanR W Tsien
Apr 1, 1994·Neuron·C C Kuo, B P Bean
Aug 12, 1999·Anesthesiology·B Rehberg, D S Duch
Dec 22, 1999·Trends in Pharmacological Sciences·D BelelliJ J Lambert
Apr 27, 2001·Anesthesia and Analgesia·G HaeselerM Leuwer
Nov 1, 1966·The Journal of General Physiology·C M Armstrong
Dec 18, 2001·Science·D RenD E Clapham
Aug 14, 2002·British Journal of Anaesthesia·J P Dilger
Dec 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rachel JurdUwe Rudolph
Feb 5, 2003·The Journal of General Physiology·Michael F Sheets, Dorothy A Hanck
Aug 13, 2003·The Journal of General Physiology·Wei XiongGordon F Tomaselli
Sep 15, 2004·The Journal of General Physiology·Alexey KuzmenkinAna M Correa
Nov 20, 2004·Science·Roderick Mackinnon
Apr 26, 2005·Biophysical Journal·Evgeny PavlovRobert J French
Aug 30, 2005·Trends in Pharmacological Sciences·Hugh C HemmingsNeil L Harrison
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Nov 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Clay M Armstrong
May 19, 2007·The Journal of Physiology·Michael F Sheets, Dorothy A Hanck
Jun 16, 2007·The Journal of Pharmacology and Experimental Therapeutics·Wei OuyangHugh C Hemmings
Jun 23, 2007·Anesthesiology·Wei OuYang, Hugh C Hemmings
Oct 24, 2007·Biophysical Journal·Yu A KaulinM Covarrubias
Feb 27, 2008·The Journal of General Physiology·Kevin DoughertyManuel Covarrubias
Apr 22, 2008·Nature Reviews. Neuroscience·Nicholas P Franks
Dec 18, 2008·The Journal of General Physiology·Yukiko Muroi, Baron Chanda
Feb 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anna Y ZechariaNicholas P Franks
Nov 26, 2009·Anesthesia and Analgesia·Yun WengJames M Sonner
Jul 6, 2010·Journal of Medicinal Chemistry·Michael A HallRoderic G Eckenhoff
Oct 12, 2010·Channels·Jose A De Santiago-CastilloJorge Arreola
Oct 13, 2010·The Journal of General Physiology·Manoel Arcisio-MirandaBaron Chanda
Jul 12, 2011·Nature·Jian PayandehWilliam A Catterall
Apr 5, 2012·The Journal of Physiology·William A Catterall
Apr 6, 2012·Frontiers in Pharmacology·Karl F Herold, Hugh C Hemmings

❮ Previous
Next ❯

Citations

Aug 18, 2018·The Journal of General Physiology·Caitlin Sedwick
Jul 19, 2018·The Journal of General Physiology·Yali WangYan Xu
Sep 1, 2019·Marine Drugs·Rocio K Finol-UrdanetaRobert J French
Sep 1, 2019·Pharmacological Reviews·Nicholas DenommeGeorge A Mashour
Dec 22, 2020·Frontiers in Cellular Neuroscience·Jinglei XiaoBuwei Yu
Aug 5, 2021·The Journal of General Physiology·Paweorn AngsutararuxJonathan R Silva

❮ Previous
Next ❯

Software Mentioned

Excel
IonChannelLab
Clampfit
rRESPA
NavMs
LigPrep
Protein Preparation Wizard ( Schrödinger
NAMD
pCLAMP
Origin

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.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Annika F BarberManuel Covarrubias
Proceedings of the National Academy of Sciences of the United States of America
Monica N KindeYan Xu
© 2022 Meta ULC. All rights reserved