The movement of ions across the cell membrane is essential for many biological processes, such as the transfer of signals through neurones, the stimulation of skeletal muscle and the production of healthy mucus. As with all small molecules, ions can either move across the cell membrane down their concentration gradient (through facilitated diffusion) or against it (through active transport). The lipid bilayer is impermeable to ions and so they must rely on transport proteins to move them across the cell membrane. These transport proteins can be grouped into several different types: ion channels, carrier proteins and ion pumps.
All ion transporting proteins have a membrane spanning region mostly composed of α-helices. These are made up of amino acids with hydrophobic side chains which stick out of the side of the helix and anchor the protein to the lipid membrane through hydrophobic interactions. The hydrophilic peptide groups are on the inside of the protein, allowing ions to lose their water shell when entering the protein and form electrostatic interactions with the peptide groups instead.
These move ions down their concentration gradient and are the fastest type of transport protein as they do not need to undergo a conformational change. Ion channels can be highly selective (e.g. only transporting Na+ ions) or more general, such as allowing through any cation. There are two main types of ion channels: gated and non-gated. Non-gated channels, such as the K+ channels involved in maintaining resting potential in neurones, allow ions through at all times, provided there is a concentration gradient for them to move down. Gated channels will only ‘open’ under the correct circumstances, such as a certain membrane potential (voltage gated channels) or when an activating ligand binds to the channel (ligand gated channels).
Ion channels rely partly on the size of ions (ionic radius) to determine which ion can pass through them- e.g. Na+ ions are smaller than K+ ions and the Na+ ion channel pore is too small for K+ ions to pass through easily. However, this is little use for distinguishing between ions of a similar radius such as Na+ and Ca2+ or for K+ channels, as the smaller Na+ ions could easily fit through the pore in a K+ channel. Instead, channels use a selectivity filter to determine which ion can pass through the pore. This is a series of a few, highly conserved, amino acids at the entrance to the pore, one on each subunit (e.g. in K+ channels the selectivity filter is the series Thr-Val-Gly-Tyr-Gly).
When ions enter a channel pore they must first lose their shell of water molecules and form new electrostatic interactions with the oxygen atoms of the carbonyl groups in the selectivity filter. It requires energy for an ion to lose its water shell so this will only happen if the new interactions it forms are more energetically favourable. In the case of the K+ channel, the oxygen atoms of the selectivity filter are ideally positioned to form interactions with K+ ions but not with Na+ ions as they are too small. This makes it energetically unfavourable for Na+ ions to enter a K+ channel and so it is very unlikely to occur.
These contain voltage sensing α helices made up of positively charged amino acid residues (each third residue has a positively charged side chain). When the channel is closed, the positively charged α helices are attracted to the negative charges on the cytosolic side of the membrane, keeping the channel in a closed conformation, with the ‘gate’ segment of the protein blocking the channel pore.
When the cytosol becomes more positive (such as during depolarisation of a neurone), the voltage sensing α helices are repelled and move towards the exoplasmic side of the membrane, inducing a conformational change in the gate segment of the ion channel and allowing ions to move through the pore. After a very short amount of time (0.5-1.0ms for Na+ channels, slightly longer for K+ channels), the voltage sensing helices return to their original position and the channel inactivating segment moves to block the pore. After repolarisation has taken place and the membrane is back to its resting potential, the channel inactivating segment is displaced and the channel returns to its original conformation.
As with most ion channels, ligand gated channels are usually very highly specific for one or two particular species of ion, e.g. the acetylcholine receptor at neurone synapses which transports Na+ and K+ ions. Acetylcholine diffuses across the synapse and then binds to the extracellular domain of the receptor, which induces a conformational change in the ion channel so that ions can pass through it. This conformational change is believed to be the rotation of α helices within the channel pore so that the large hydrophobic residues that were previously facing into the pore are replaced by small hydrophilic residues which can interact with the ions and allow them to move through the channel.
These can transport many different types of small molecules, not just ions and they are much slower than channels as they undergo a conformational change every time they move a molecule across the lipid bilayer. (Carrier proteins transport molecules/ion at a rate of 1-1000 per second whereas ion channels transport ions at up to 10^8 per second) There are three main types of carriers:
• Uniporters- move one molecule at a time, using facilitated diffusion
• Symporters- move two types of molecule in the same direction simultaneously, e.g. the Na+/glucose symporter.
• Antiporters- transport one type of molecule in one direction while moving another in the opposite direction
Symporters and antiporters use secondary active transport: the movement of one type of molecule down its concentration gradient is used to power the transport of another molecule against its concentration gradient.
These use primary active transport to move ions against their concentration gradient. The energy required to do this is gained by the hydrolysis of ATP, which is used to drive a conformational change in the pump and to push the ion/molecule to the other side of the membrane. Pumps can be divided into four categories, three of which are used exclusively for ion transport.
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