Voltage-Gated Sodium Channels: Biophysics, Pharmacology, and Related Channelopathies

نویسندگان

  • Eleonora Savio-Galimberti
  • Michael H. Gollob
  • Dawood Darbar
چکیده

Voltage-gated sodium channels (VGSC) are multi-molecular protein complexes expressed in both excitable and non-excitable cells. They are primarily formed by a pore-forming multi-spanning integral membrane glycoprotein (α-subunit) that can be associated with one or more regulatory β-subunits. The latter are single-span integral membrane proteins that modulate the sodium current (I(Na)) and can also function as cell adhesion molecules. In vitro some of the cell-adhesive functions of the β-subunits may play important physiological roles independently of the α-subunits. Other endogenous regulatory proteins named "channel partners" or "channel interacting proteins" (ChiPs) like caveolin-3 and calmodulin/calmodulin kinase II (CaMKII) can also interact and modulate the expression and/or function of VGSC. In addition to their physiological roles in cell excitability and cell adhesion, VGSC are the site of action of toxins (like tetrodotoxin and saxitoxin), and pharmacologic agents (like antiarrhythmic drugs, local anesthetics, antiepileptic drugs, and newly developed analgesics). Mutations in genes that encode α- and/or β-subunits as well as the ChiPs can affect the structure and biophysical properties of VGSC, leading to the development of diseases termed sodium "channelopathies".  This review will outline the structure, function, and biophysical properties of VGSC as well as their pharmacology and associated channelopathies and highlight some of the recent advances in this field.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Voltage-Gated Sodium Channels Modulation by Bothutous Schach Scorpion Venom

Buthotus schach is one of the dangers scorpion in Iran that belong to the Buthidae family. Toxins are existing in venom scorpion, modulate the ion channels by blocking or opening the pore of the channel or by altering the voltage gating and useful as pharmacological tools. In the present study, we investigated the effect of venom and its obtained fractions by gel filtrations on electrophysiolog...

متن کامل

Editorial: Recent Advances in Voltage-Gated Sodium Channels, their Pharmacology and Related Diseases

Because of their fundamental role in generating electrical impulses in many excitable tissues, sodium channels were among the first voltage-gated ion channels to be extensively investigated. Neurons bathed in a physiological solution containing 150 mM sodium ions respond to a threshold electrical stimulus by generating an action potential, whereas such a response is abolished in a Na+-free medi...

متن کامل

Functional interaction between S1 and S4 segments in voltage-gated sodium channels revealed by human channelopathies

The p.I141V mutation of the voltage-gated sodium channel is associated with several clinical hyper-excitability phenotypes. To understand the structural bases of the p.I141V biophysical alterations, molecular dynamics simulations were performed. These simulations predicted that the p.I141V substitution induces the formation of a hydrogen bond between the Y168 residue of the S2 segment and the R...

متن کامل

Review article Channelopathies: ion channel defects linked to heritable clinical disorders

Electrical signals are critical for the function of neurones, muscle cells, and cardiac myocytes. Proteins that regulate electrical signalling in these cells, including voltage gated ion channels, are logical sites where abnormality might lead to disease. Genetic and biophysical approaches are being used to show that several disorders result from mutations in voltage gated ion channels. Underst...

متن کامل

Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels

Voltage-gated sodium channels (Nav) are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disor...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2012