I have been reading a book called “Principles of Neural Science” by Eric Kandel. I thought it would be a good idea to write a summary of a chapter that I read recently and tell you all about one the most important structures present in the cytoplasmic layer – Ion Channel. Ion channels allow the movement of ions across cell membranes, and therefore fundamental physiological processes such as muscle contraction.
Ion channels are membrane protein complexes. They are embedded in the lipid bilayer which is made up mostly of phospholipids, which have a hydrophilic head and two hydrophobic tails. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. They make good barriers because they are only a few nanometres thick, they are impermeable to most water-soluble (hydrophilic) molecules and are particularly impermeable to ions.
Definition: Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane by allowing the flow of ions down their electrochemical gradient.
Concept of Open/Close
Ion channels provide a high conducting, hydrophilic pathway across the hydrophobic interior of the membrane. The channel, or pore structure, is said to catalyze the ‘reaction’ of transporting charged molecules across a low dielectric medium. The ‘catalytic site’, the central channel, is either open or closed. The conformational change between closed and open state is called gating. Channel gating is controlled by external factors like enzymes are controlled by modulators and effectors.
Types of Ion channels
There are over 300 types of ion channels in a living cell. Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, the number of gates (pores) and localization of proteins.
- Ligand gated channels
- Voltage gated channels transmembrane potential
- Second messenger gated channels
- Mechanosensitive channels
- Gap junctions
Structure of a channel
Channels differ with respect to the ion they let pass (for example, Na+, K+, Cl−), the ways in which they may be regulated, the number of subunits of which they are composed and other aspects of structure. All ion channels are complexes of transmembrane proteins, sometimes they contain cytoplasmic subunits, often they are glycosylated. The 3-D structure of most ion channels is not known, with two notable exceptions, porins and a K-channel, both of bacterial origin. There exists, however, a multitude of biochemical and functional data, combined with mutagenesis experiments that give information about the transmembrane topology of these proteins, dividing it into transmembrane segments and extramembraneous loops/domains. Often size and location of loops on one side or the other of the membrane can be determined by chemically modifying the protein and analyzing which amino acids have been modified.
For example: Nicotinic Acetylcholine Receptor – nAChR
The structure of nicotinic acetylcholine receptor, has been determined to 0.9nm resolution by cryo-electron microscopy. The nAChR is a heteromeric glycoprotein complex composed of five integral membrane proteins in a stoichiometry of α2βγδ.
The five subunits are arranged in a circular fashion around a central hole that provides an ion pathway across the post-synaptic cell membrane. The pentameric complex has a fivefold pseudo-symmetry because its subunits are not identical. Acetylcholine binding induces the opening of the channel.
Problems associated with Ion channels
There are a number of chemicals and genetic disorders which disrupt normal functioning of ion channels and have disastrous consequences for the organism. Genetic disorders of ion channels and their modifiers are known as Channelopathies.
- Human hyperkalaemic periodic paralysis (HyperPP) is caused by a defect in voltage dependent sodium channels.
- Dendrotoxin is produced by mamba snakes, and blocks potassium channels.
That is it for now. I hope you liked what you read. If you are interested, I could always find more references and papers to support the above data.