<P> Voltage - gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains . Each domain contains 6 membrane spanning alpha helices . One of these helices, S4, is the voltage sensing helix . The S4 segment contains many positive charges such that a high positive charge outside the cell repels the helix, keeping the channel in its closed state . </P> <P> In general, the voltage sensing portion of the ion channel is responsible for the detection of changes in transmembrane potential that trigger the opening or closing of the channel . The S1 - 4 alpha helices are generally thought to serve this role . In potassium and sodium channels, voltage - sensing S4 helices contain positively - charged lysine or arginine residues in repeated motifs . In its resting state, half of each S4 helix is in contact with the cell cytosol . Upon depolarization, the positively - charged residues on the S4 domains move toward the exoplasmic surface of the membrane . It is thought that the first 4 arginines account for the gating current, moving toward the extracellular solvent upon channel activation in response to membrane depolarization . The movement of 10--12 of these protein - bound positive charges triggers a conformational change that opens the channel . The exact mechanism by which this movement occurs is not currently agreed upon, however the canonical, transporter, paddle, and twisted models are examples of current theories . </P> <P> Movement of the voltage - sensor triggers a conformational change of the gate of the conducting pathway, controlling the flow of ions through the channel . </P> <P> The main functional part of the voltage - sensitive protein domain of these channels generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence, interchangeable across a wide variety of cells and species . A similar voltage sensor paddle has also been found in a family of voltage sensitive phosphatases in various species . Genetic engineering of the paddle region from a species of volcano - dwelling archaebacteria into rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced . This "modularity" allows use of simple and inexpensive model systems to study the function of this region, its role in disease, and pharmaceutical control of its behavior rather than being limited to poorly characterized, expensive, and / or difficult to study preparations . </P>

Difference between voltage gated channels and ligand gated channels