# Structural Biochemistry/Action Potential

The action potential is the brief electrical impulse that is responsible for the propagation of information down the axon of a neuron. Some important concepts involved with the action potential are the membrane potential, resting potential, threshold. The membrane potential is the difference in electrical potential inside and outside the cell. The resting potential is the membrane potential of a neuron when the neuron is at rest and not receiving any excitatory or inhibitory signals. In many neurons, the resting potential is approximately –70 mV. The threshold is the membrane potential that has to be reached to produce an action potential. An action potential is an all or nothing phenomenon. It either reaches the threshold and produces an action potential or it doesn’t.

## Process

The first step in the action potential is for the neuron’s membrane potential to reach the threshold. This change in the membrane potential can be caused by a variety of factors including excitatory stimulation by another cell or neuron. An increase in the membrane potential is also called a depolarization. After the threshold is reached, voltage-gated sodium channels open, and sodium ions enter the cell, increasing the resting potential. As the voltage continues to increase, the voltage-gated potassium channels open as well, and potassium ions leave the cell. However, the membrane potential continues to increase as the sodium ions are still entering the cell. When the membrane potential reaches its peak, the action potential is attained, and the sodium channels become refractory and no more sodium ions enter the cell. Potassium ions continue to leave the cell, and the membrane potential slowly decreases towards the resting potential. This decrease in the resting potential is called a hyperpolarization. At the resting potential, the potassium channels close and the sodium channels “reset” so that they can open again if the threshold is reached. Since all the potassium channels don’t close as soon as the resting potential is reached, extra potassium ions leave the cell, decreasing the membrane potential past the resting potential. The membrane actually undergoes an afterhyperpolarization, a drop in the membrane potential past the resting potential. Eventually, the membrane potential returns to the resting potential as the potassium ions diffuse back into the cell as the cell membrane is quite permeable to potassium ions. Sodium-potassium transporters pump sodium ions out of the cell and pump potassium ions into the cell.
Mechanism (Refer to diagram)
The resting potential is set by the sodium potassium pump which pumps 3 Na+ and 2K+ in using the energy of 1 ATP. This energy is required because the ions are being pumped against their concentration gradient. Resting potential lies between -60 to -80 mV. At resting potential, no signals are being sent across the membrane. Depolarization is the second step in this mechanism and occurs when the cell becomes less negative because Na+ voltage gated channels have opened and Na+ ions are now entering the cell causing a reduction in the magnitude of the membrane potential. Once the membrane potential reaches -55 mV, it has reached threshold which will trigger an action potential. The third step is called the rising phase where more Na+ voltage gated channels open which causes the cell to become less negative. It brings a positive charge to the cell which further enhances depolarization. More sodium channels open, resulting in a positive feedback loop. The following step is called the falling phase because eventually, Na+ voltage gated channels get inactivated and block additional sodium from entering. Mean while, the K+ voltage gated channels start to open and hyperpolarization takes place. Hyperpolarization causes an increase in the magnitude of the membrane potential resulting in making the cell more negatively charged. The last part of this mechanism is called the undershoot because the Na+ voltage gated channels close completely while K+ channels also begin to slowly close. And this returns the membrane potential back to rest just as in the first step of the mechanism.
Na+/K+ Pump Mechanism The ion pumps, with bound to ATP, binds 3 intracellular Na+ ions. The ATP is hydrolyzed, leading to phosphorylation of the pump and subsequent release of ADP. There is a conformational change in the pump takes place exposing the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released. The pump then binds 2 extracellular K+ ions, which causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K+ ions into the cell. The dephosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released. ATP binds, and the process starts again.
Conduction of Action Potential
As an action potential travels down an axon, it is regenerating the depolarization. The action potential is transferred to neighboring regions, conducting action potential throughout the entire axon. While an action potential is being conducted in a particular region of the axon and is undergoing falling phase, the area behind it is hyperpolarizing and undergoing the falling phase. This area is known as the repolarized zone caused by the outflow of potassium ions. As a result, the inactivated Na+ channels behind the area of depolarization prevent any action potentials from traveling backwards, making them uni-directional.
Properties
1. Action potential is always depolarizing.
2. Action potential's amplitude is independent of stimulus pathway.
3. Action potential has all or none response. If the frequency reaches or passes the threshold, action potential occurs. If it falls under the threshold, no action potential occurs.
4. Amplitude does not decay with distance. It is indeed transferred equally, without any loss, across the axon.
5. There is an absolute refractory period and a relative refractory period.
6. At rest channels for sodium and calcium are closed
7. Membrane is selectively permeable to potassium the most
8. Osmotic pressure is opposed by electrostatic pressure to reach equilibrium for balancing the concentration ions.

## Effects of Axon Structure

The diameter of an axon influences the speed of an action potential. The larger the width of an axon, the less resistance it provides to the current of an action potential. It acts analogous to how a water hose would, the wider the diameter of a hose offers less resistance to the flow of water. As a result, action potentials are conducted much faster. Another factor that contributes to the speed of action potential are myelin sheaths. Myelin sheaths are made by two types of glia, Schwann Cells in the peripheral nervous system and oligodendrocytes in the central nervous system. Myelin acts as an insulator for the axon and increases the length over which an action potential can be effective. This form of insulation allows the depolarizing current of an action potential to reach threshold sooner. The only problem with insulation is that axons now no longer have access to the environment or extracellular space. The only areas on an insulated axon that do allow for interaction are gaps in the myelin sheaths called Nodes of Ranvier. Action potentials are only formed at these nodes because this is the area where the exposed Na+ voltage gated channels are located. One node will undergo the rising phase of an action potential and the current produced will travel immediately to the next node where the membrane will then be depolarized and action potential will be regenerated. The process in which the action potentials and depolarization jump from node to node is called saltatory conduction.

## Reference

Carlson, Neil R. Physiology of Behavior. Boston: Pearson Education, Inc., 2007.
Reece, Jane B. Campbell Biology, 2011
Levinthal, Charles, "Drugs, Behavior, and Modern Society", Pearson Education, Inc., 2008