Since membrane proteins are found at the interface between cells, unsurprisingly one of their key functions is transport of molecules and ions across the membrane, since many can’t make their way on their own.
The main properties of molecules that determine how they may be transported across a membrane are solubility, size and charge.
Diffusion = the spread of particles from a region of higher concentration to a region of lower concentration, until the particles are evenly spread out.
Diffusion takes place when you use a spray in a room, for example. The particles in the spray move randomly, knocking each other, which results in them spreading throughout the room gradually, from high concentration to low concentration. Therefore, diffusion acts down (or along) a concentration gradient.
It is important to know what affects the rate of diffusion. These are:
1. Surface area – the greater the surface area, the faster diffusion will occur
2. Difference in concentration – the higher the difference (the steeper the gradient), the faster diffusion will take place
3. The thickness of the exchange surface – the thicker the exchange surface, the slower the rate of diffusion.
Of course there are other factors such as temperature (increased kinetic energy results in faster diffusion) and the diffusion pathway (distance). The latter is a side effect of (3.) The thickness of the exchange surface, in some respects.
Osmosis is the diffusion of water across a semi-permeable membrane. The “concentration” of water is referred to as water potential. So osmosis is the movement of water from a higher water potential to a lower water potential across a membrane.
For osmosis to occur it is essential that there is a semi-permeable membrane separating two environments with a different solute concentration. The solute must be unable to cross the membrane (molecules too big), but the water molecules are free to pass through and lead to an equilibrium. In the above image, the right side of the beaker has a higher water potential than the left side, so water moves in from right to left.
You must also learn the term isotonic. A solution is isotonic when it has the same water potential as another solution. An example is Ringer’s solution which has the same water potential as blood plasma, so can be used to keep tissues alive.
In some cases, diffusion is aided by certain proteins. This is called facilitated diffusion. The responsible proteins speed up diffusion of substances which would otherwise take longer to pass through the plasma membrane. The key points about facilitated diffusion which differentiate it from active transport (which also uses proteins):
-it occurs down a concentration gradient
-it uses no metabolic energy
Two kinds of protein achieve facilitated diffusion: carrier proteins and ion channels. Carrier proteins transport substances from one side of the membrane to the other, usually by co-transport. For example, glucose is transported along with an Na+ ion.
Ion channels are proteins with gates that can be open or closed to allow or stop certain ions from entering, e.g. Na+ (sodium) and K+ (potassium) ions.
When gated channels are controlled by the presence of a chemical, they are termed ligand-gated channels, while those that respond to changes in ion concentration are voltage-gated channels. The latter are central to nervous signal transmission.
An example of a simple channel protein is aquaporin that enables passage of water molecules.
Aquaporins allow the passage of water molecules in a single file. They prevent the passage of other small ions dissolved in water because they have a positive charge in the middle of the channel that repels them.
Unlike diffusion, osmosis and facilitated diffusion, active transport requires energy in the form of ATP (adenosine triphosphate), and moves substances against a concentration gradient (from a lower concentration to a higher concentration). This process is essential in removing of all toxins from the body, as well as the movement of rare chemicals.
Active transport is achieved by specific carrier proteins in the plasma membrane, and relies on adequate oxygen supply (which results in ATP being available). Here’s a quick video that shows the process:
There are certain cells which carry our active transport more than others, for example in the kidney. These cells have special adaptations, such as microvilli for increased surface area, hence more carrier proteins available, as well as many mitochondria for the production of ATP.
Transporting molecules in this way relies on a change in conformation of the transporter protein. This is where the use of ATP energy goes towards. The two possible conformations of the transporter protein correspond to the side of the membrane where the target molecule is transported to.
In sodium-potassium gated channels, the binding of sodium ions causes phosphorylation of the pump. This is where ATP is used. In response, the protein changes conformation. This shifts its affinity to sodium ions and releases them to the other side of the membrane. When potassium ions bind as a result, it causes dephosphorylation, releasing the ions to the other side and starting the cycle anew from the original conformation.
Not only is this central to nervous transmission, as we’ll see in this topic, but also to other systems including kidney function, absorption of glucose in the intestine and simply maintaining the osmotic balance in the body. Maintain these ion gradients costs metabolism up to a quarter of all energy expenditure.
Adrenaline is secreted by the adrenal glands in times of stress or exercise. It has the same effect as glucagon. Both of these hormones act via a second messenger. That is, they bind to the plasma membrane of cells and exert their influence from the outside by causing a cascade of enzymatic reaction events inside the cell which ultimately end up in their response. They chicken out of it, don’t blame the messenger.
The second messenger model includes adenylate cyclase, cyclic AMP (cAMP) and protein kinase. Epinephrine is another word for adrenaline.
In this way, membrane proteins play a key role in sending signals between cells that regulate function. Aside from the G protein pathway, other intracellular responses enacted by communication through membrane receptors include simple enzyme activation, change in uptake or secretion of molecules, or even a rearrangement of the cytoskeleton or activation of proteins involved in gene transcription.
Let’s delve into the basics of nervous transmission by looking at a motor neurone. Here is the structure of a myelinated motor neurone:
Labelled “insulating sheath”, the myelin sheath is responsible for protecting the electrical impulses that run across the neurone.
But first, what happens in a resting state where no impulses are being sent?
This is the resting potential where the membrane permeability differentiates between sodium (Na+) and potassium (K+) ions so that at any given time there are more Na+ ions outside than inside and more K+ ions inside than outside.
According to these electrochemical gradients, Na+ ions should move back inside to balance out their concentration (equilibrate) while K+ ions should move back outside the membrane until the concentrations are equal inside and out. This clearly isn’t the case, so what gives?
Found on the membrane there are Na+/K+ pumps which carry out active transport against the electrochemical gradient of these ions. The resting potential of the membrane is negative on the inside and positive on the outside – but how? Aren’t both sodium and potassium ions positively charged? This is achieved by the pump transferring 3 Na+ ions out while taking only 2 K+ ions in. This is where the difference comes from.
Now we know that in the absence of an action potential the resting potential of the neurone membrane is negative (about -70 mV; millivolts). What precedes an action potential and how does it unfold?
A stimulus may depolarise the membrane by opening up Na+ channels for those ions to rush into the axon. An action potential will occur only if the depolarisation passes a certain threshold. For example, if it reaches -60 mV up from -70 mV it will not trigger an action potential with a threshold of >-45 mV.
Therefore, the power of an action potential is not proportional to that of its stimulus. It either happens or it doesn’t. This is called the all-or-nothing principle.
This is how the voltage of the axon membrane changes during an action potential:
The rush of Na+ ions into the membrane during depolarisation causes the voltage to become positive. Note how only the depolarisation that has passed the threshold initiates an action potential.
Repolarisation occurs when Na+ channels begin to close and K+ channels open, resulting in a rush of K+ ions out of the axon. Before all the K+ channels close, hyperpolarisation occurs which briefly sees the voltage drop below the resting potential level.
This also represents the refractory period where either no stimulus however strong can initiate another action potential (absolute refractory period), or a stimulus slightly greater than usual would be required for an action potential to occur (relative refractory period).
Finally the resting potential is achieved.
The Myelin Sheath
This insulating sheath made up of Schwann cells conducts electricity and therefore is key in ensuring fast signal transmission. The signal is able to “jump” along the axon without losing its strength:
Each pink cell is a Schwann cell. Due to the jump-like action, this conduction is termed saltatory conduction. Factors that affect conduction other than myelination and saltatory conduction (which allow speeds many times faster compared with no myelination) include temperature and axon diameter.
Since chemical movement (kinetic energy) relies on temperature, an optimal temperature maximises conduction. A temperature lower than this would slow it down. This is due to a slower opening of sodium channels for example, and also a slower inactivation resulting in a longer delay.
Axon diameter affects conduction in terms of resistance. The signal travelling along a thin axon encounters the resistance of the axon membrane, while for an axon with larger diameter, a smaller proportion of the signal is met with resistance in this way. The signal carried on the inner section of the axon has no resistance and can travel faster.
A synapse is the site of communication between the end of an axon and the beginning on a dendrite. It can also be between a neuron and a non-neuron cell such as a muscle cell. In the olden days people used to think that there were no gaps between neurons, and they just extended continuously throughout the body (silly eh?). Now we know better, much better. More for you to learn!
Let’s just get the overall picture first: a signal may be transmitted from one neurone to another via axons and dendrites. A sending neurone passes the signal to a receiving neurone which may pass it on to another receiving neurone, thus becoming itself a sending neurone…
Clearly, each nerve cell (= neurone) only has one axon but multiple dendrites. How does this regulate the way in which certain signals are deemed to pass the threshold required for them to be passed along as opposed to them ceasing there?
There are 2 ways: either multiple signals are sent via the same synapse in a short space of time, or single signals are sent via synapses at different locations. Therefore, the first is called temporal summation while the second is called spatial summation. Summation simply refers to the sum of signals sent to reach the threshold for transmission.
Another nugget to be gotten out of the way: the signal transmitted is always axon –> dendrite, unidirectional, because specific neurotransmitter receptors are only found on the dendrites!
Now let’s delve into the details…
The first is a pre-synaptic neurone, the second is a post-synaptic neurone. Before and after the synaptic gap itself, or the synaptic cleft. The action potential reaching the pre-synaptic neurone causes some calcium channels which respond to voltage to open. These are called voltage-gated ion channels. Essentially this step converts the electrical energy into chemical energy. Ca+ ions rush inside.
As a result, vesicles (membrane-bound spaces containing a specific compound) migrate towards the outer edge of the neurone membrane and fuse (exocytosis) so that their contents – neurotransmitters in our case (you know, the good stuff like serotonin, oxytocin, dopamine, etc.) – are released into the synaptic gap.
Specific neurotransmitter receptors found on the post-synaptic neurone bind the neurotransmitters causing Na+ channels to open. Na+ ions rush into the post-synaptic neurone. If they’re angry enough (we’re talking about a steep electrochemical gradient of course), an action potential will be initiated and carried forward. Chemical energy has once again been converted into electrical energy. Magic.
Not all synapses are excitatory and encourage a signal to be carried forward. Some are inhibitory and prevent an action potential being carried forward. A common signal molecule (neurotransmitter) for this is GABA. Upon binding to receptors on the membrane, it triggers an uptake of chlorine ions into the cell, or a release of sodium ions out of the cell; both of which shift the transmembrane potential downwards, making it more negative.