The majority of all action potentials are generated in the axon hillock. However in sensory neurons the action potential is generated by the peripheral (axonal) process, just proximal to the receptor region. These areas are also known as the trigger regions. An action potential is generated due to membrane potential reaching threshold due to a graded potential. Threshold is a membrane potential at which the membrane in the trigger region reaches approximately -55mV, a depolarization of about 15 mV. At this point action potentials become self propagating. This means that one action potential automatically triggers the neghboring membrane areas into producing an action potential. Thus once threshold is reached action potentials always propagate down the axon to the synaptic or secretory regions of the axon. The actual process of the action potential generation occurs in four steps, consecutive, but overlapping. These steps are all opening and/or closing of ion gates, and subsequent changes in membrane potentials.

1) The first step is the resting state, where all active ion channels are closed. Almost all voltage gated sodium and potassium gates are closed. However some potassium is leaking out via leakage channels, and even smaller amounts of sodium are diffusing in.

2a) This phase is actually consists of two substeps. As the trigger region membrane is depolarized to threshold voltage gated sodium channels begin to open. By the time threshold potential is reached enough voltage gated sodium channels (vgsc?s) are opened that the potential is now self generating, being driven on by the influx of Na⁺. With the vast majority of the vgsc?s opened Na⁺ floods into the cell, further depolarizing the cell, and increasing the membranes permeabliliy to sodium by over 1000 times. Eventually the cell lets in so many positively charged sodium ions that the membrane potential goes from -70mV to +30mV.

2b) As the membrane potential reaches 0mV, and the cell interior becomes more and more positive, sodium entry becomes less rapid, as the electrical gradient starts to repel the ions. Furthermore in less than a milisecond of reaching threshold the sodium gates begin to close, albeit slowly. This additionally causes the membrane to start to loose permeablility with regard to the sodium ions. As the net influx of sodium declines, and then finally stops, the membrane has reached it?s maximum depolarization at about +30mV.

3) As the membrane potenial approachs +30 mV, voltage gated potassium channels open and positively charged potassium ions begin to flow out of the cell. This begins to repolarize, the cell by reducing the excess internal positive charge and moving the membrane potential closer to the resting potential. At this point the cell is basically impermeable to sodium and very permeable to potassium which rapidly flows out of the cell down both it?s electrical (initially) and chemical gradients.

4) Potassium efflux (exiting) continues past the resting potential of -70 mV due to the slow closing voltage gated potassium channels. This causes a hyperpolarization know as undershoot which takes the membrane potential to around -75mV. Soon afterward the cell returns to resting potential via the standard membrane proteins.

As stated earlier action potentials are self generating once threshold is reached. As sodium ions rush in during the depolarizing phase of the action potential a large concentration of sodium ions accumulates in that region of the axon. These sodium ions have a repulsive effect on each other and other positively charged ions in the cytoplasm. They cause positive charges, and other sodium ions to diffuse away from the large accumulation excess positve charge, and simultaneously draw more negative charges toward them (or if looked at another way are themselves drawn to the surrounding regions or negative charge). This causes a flow of positive charge outward from the action potential site, which causes a depolarization of the adjacent membrane. On the outside of the membrane, the large infux of sodium ions has left a slight negative charge just outside the membrane. This is quickly filled in by surrounding positive charges. These positive charges must come from somewhere, and some of them come from areas on adjoining membrane. This causes a slight negative charge to be on the outside of the adjoining membrane where the replacement or equilizing positive charge came from. This patch of external negative charge coincidentaly is generally exactly opposite of the newly depolarized internal membrane due to the nature of ion flow (current). This combination sets up the idea of current flow in the axonal membrane, and it is this current that causes the adjacent membranes to depolarize and reach threshold. This causes adjacent membrane patches to have action potentials and the potential is thus propagated all the way down an axon. After an action potential the membrane goes through repolarization, thus a wave of repolarization chases the wave of depolarization down the axon. Action potentials flow in only one direction. This is because they are generated at the trigger region which is generally the start of the axon in the axon hillock. However when sodium enters the cell during depolarization it flows in both directions toward the end of the axon (the direction of propagation) and backward toward the cell body. The back flow has little effect at this point however. Further down the axon on the other hand on might ask why doesn?t the flow of ions cause an action potential backwards the way it came. After all the sodium ions don?t just depolarize adjacent membrane in the forward direction, the current flows in both directions both forward and backward. One reason is that the preceeding area of axon is still depolarized, and current, tends to follow the path of least resistence, toward an area of resting potential. As one area of axon is being depolarized and letting in sodium rapidly (because it has just reached threshold) the preceeding area of membrane is still in the depolarizing phase of its action potential, thus that area of membrane may not be immediately stimulated to produce another action potential anyway. This period is called the absolute refractory period. This period coresponds to the sodium channels being open and the fact that the membrane is in the middle of one action potential all ready. The membrane is incapable of responding to another stimulus no matter how strong it is. In a period called the relative refractory period that follows the absolute refractory period, the axons threshold is drastically increased, thus while not being impossable to generate another action potential, it requires a much stronger stimulus. This period is due to the sodium channels being closed and the potassium channels being open. So in this manner exceptionally strong stimuli can cause more frequent generation of action potentials.

Action potentials must be able to progagate and move very fast in order to cover the great distances that nerve impulses must travel. For instance if a person steps in cold water and then quickly removes their foot the signal must travel twice the persons body length, before the muscles begin to react by pulling the foot out of the water. The initial response must travel from the foot to the spinal cord, up the spinal cord to the brain where it is processed, and then sent back to the spinal cord, down the spinal cord and eventually to the muscles which effect the withdrawal of the foot. When one thinks about how fast people actually respond to such stimuli, action potential speed becomes very important, and is recognized to be extremely fast. The fastest neurons are those that are in pathways in which speed is essential such as certain reflex pathways. These neuron can transmit impulses up to 100 meters per second. Axons that serve internal organs are generally slower, but such a reduction in speed is hardly a handicap for such systems. The speed of the impulse conduction is largely dependent on the axon diameter, and it?s degree of myelination. As the axon increases in diameter (and thus cross sectional area) the resistance to ion flow decreases, allowing the ions (and consequently the current) to flow faster. The degree of myelination caused by schwann cells and oligodendrocytes also greatly effects conductance speed of action potentials. Myelin acts as an insulator, preventing almost all loss of charge from the axon. In myelinated axons, only at nodes of ranvier can the current cross the membrane. This means that once an action potential is begun, it doesn?t cause adjacent membrane to depolarize since that area insulated by myelin. Instead the charges flow rapidly along the axon until the next node of ranvier (where many voltage gated ion channels are located) where it again induces an action potential, a distance of approximately 1mm. It is in this way that myelination appears to make the current "jump" from node to node. This kind of conduction is called saltatory conduction.

Action Potentials Vs. Graded Potentials

The neuron communicates by nerve impulses, also known as action potentials. Neurons are not the only cells to propagate action potentials, muscle cells can also. However only axons, and thus neurons, are able to generate action potentials. An action potential is a change in membrane potential from -70 to +30mV. This is similar in many regards to graded potentials. However there are five principal differences between the two.

1) While graded potentials are decremental in strength, action potentials are an all or none response. To put it simply the strength of a graded potential is directly proportional to the strength of the stimulus that causes it. While all action potentials are the same strength. Differentiation, as in stronger or weak signals, in action potentials is therefore not mediated by intensity of the depolarizations, but by the frequency at which they occur. Thus graded potentials can be said to be AM (amplitude modulated), while action potentials can be said to be FM (frequency modulated).

2) The graded potential may last for as long as a stimulus persists. Action potentials all lasts for a short period of perhaps .15 ms.

3) Graded potentials have no threshold, very tiny or very large depolarizations or hyperpolarizations may be induced. Action Potentials on the otherhand require a large change in potential, about 15mV, in order for them to be generated.

4) Graded potentials summate, in other words they are cummulative. Action potentials have a refractory period in which no other action potential will be generated in that area of membrane. The next action potential will be exactly the same strength and duration as its predecessor. A potential at the end of an axon is the same size as one recorded at the begining of the axon.

5) Response is local in graded potentials, and spreads passively outward from area of initiation. Potentials are actively regenerated along an axon.

Once the trigger region of an axon reaches threshold the action potential becomes self generating. In other words no further outside stimulus is needed for the action potential to occur. Because the vgsc?s open in close at certain membrane potentials and over a set period of time, all action potentials on an axon are of the same intensity or strength. This is because each action potential along an axon depolarizes the membrane at the same rate and to the same extent. Thus each action potential is the same strength, whether it is near the begining or end of the axon. This also means that there is no such thing as a half strength action potential, and so action potentials are characterized by this all or none phenomenom. One either gets the complete action potential, if the stimulus causes the trigger region to reach threshold, or no action potential at all, even if threshold was missed by just a fraction of a millivolt.

An important question to ask, is what exactly determines the threshold point. One explanation is that it is the membrane potential at which the current caused by the influx of sodium is equal to the the current caused by the efflux of potassium. This generally occurs around 15 to 20 mV. At this point extra sodium ions in will cause further membrane depolarization and the opening of more sodium channels, drastically increasing the influx of sodium and its conductance across the membrane. This will also cause rapid depolarization of the membrane, and the action potential is begun.

An important question arises regarding differentiation between nerve impulses, in other words if all action potentials are the same strength how does one tell the difference between a slight touch and a punch, or a warm bath and scalding water? The answer is through frequency modulation. This basically means that the more intense the signal is supposed to be, the more action potentials that are sent down the axon, per unit of time. Hypotheticaly speaking, lets say a person sticks their finger in a warm bath. The receptor may cause the axon to fire 1 action potential per second. Now that same person sticks their finger in a pot of boiling water, that same receptor may cause the axon to fire 100 action potentials in one second (note these numbers are fictitious and used as an example only). Thus a stronger stimulus causes a stronger graded (receptor) potential, which in turn is able to not only cause an action potential but to repeatedly cause an action potential, causing them to be generated at a greater frequency.

�