An action potential is the result of a very rapid sequence of changes in the voltage across a cellular membrane. The membrane voltage, or potential, is determined at any time by the relative ratio of ions, extracellular to intracellular, and the permeability of each ion.
The response of a nerve or muscle cell to an action potential can vary according to how frequently and for what duration the action potentials are fired. An action potential requires an influx of positive ions to produce a specific change in the voltage (threshold value). It occurs after a certain degree of internal cell membrane depolarization – a positive increase in electrical charge.
What is an Action Potential?
So, what is an action potential? Many definitions tend to be quite complicated, especially when you are learning about action potentials for the first time. To completely unravel the mystery, we should first look at the meaning of the term.
The word potential, in this case, does not mean the chance of achieving something but refers to an electric potential. This is a continuous energy field more usually associated with the field of physics. In biology, potentials are found at the inner and outer edges of cell membranes.
Potential energy is stored energy, which is why it is continuous. When a ball is still, it has potential energy. When a neuron is not firing, it has potential energy. Instead of saying a cell or rather its membrane has potential energy, we say is has a resting potential.
When force is applied to a ball, it will move. The potential energy changes into kinetic energy or the energy of motion. This force is not produced by the ball but comes from an external source; it replaces potential energy with kinetic energy. When this kinetic energy runs out (and no more external force is applied), the ball comes to a stop. It then possesses potential energy once more.
In the cell membrane, charged atoms called ions cause the equivalent of motion – they cause action. When a neuron is not firing and when a cell membrane is not allowing large amounts of certain products (we will talk about these later) to enter or leave the cell, that cell has resting potential. When electrical activity is stimulated, the potential stops resting because external forces create electrical movement – an action potential.
In order to fully understand this mechanism, we also need to know more about the electrical charge – the energy field – that is associated with a resting state and an active state. An electrical charge is the result of atoms. If you know about the form of an atom – a proton and neutron nucleus with a cloud of electrons circling this nucleus – you will probably know that protons are positively charged and electrons are negatively charged. This is just a fact; there is no need to understand why.
Usually, an atom has the same number of positive protons as it does negative electrons. If it does not, it tries to join with other atoms so that these charges are similar and the atom can be stable. In a neutral state, an atom is just an atom.
When it has too many electrons it will have a negative charge and is called a negatively-charged ion. If it has too few electrons (the number of protons stays the same), the positive charge of the proton is larger and the atom is called a positively-charged ion.
These ions are extremely important when talking about electrical signaling in the form of action potentials. Cells that use action potentials are neurons and muscle cells.
Cellular Action Potential
Although usually discussed in the context of neuronal cells, action potentials also occur in many excitable cells such as cardiac muscle and some endocrine cells.
Within a population of neurons, there can be significant variability in the intrinsic electrical properties of the cell, such as resting potential, maximum firing rate, resistance to current, and width of action potentials. These variables are directly dependent upon the number, location, and kinetics of ion channels within the membrane.
Within the heart, pacemaker cells located in the SA node initiate action potentials intrinsically and rhythmically. Unlike in neurons, the majority of current in pacemaker cells gets mediated through calcium flux.
A transient current of calcium ions, mediated by T-type calcium channels, slowly depolarizes the pacemaker cell until reaching the threshold potential for L-type voltage-gated calcium channels, inducing an action potential.
The action potential is then dispersed throughout the heart by myocardiocytes, cardiac muscle cells that contract while they conduct the current to neighboring cells. Similar to action potential initiation in neurons, and in contrast to pacemaker cells, myocardiocytes initiate rapid depolarization through voltage-gated sodium channels.
Development of Action Potential
There are several pre- and postnatal maturational processes that serve to modulate action potential formation and propagation. Below, we will specifically address changes in ion concentration, ion channel density, and ion channel location. Additionally, the speed of action potential propagation along myelinated axons is increased throughout development as myelin thickens, and the distance between nodes of Ranvier lengthens.
During embryonic development, the intracellular concentration of sodium significantly decreases. Because the relative intracellular and extracellular concentrations of an ion determine the driving force of ions across the membrane, changes in ion concentration can significantly affect action potential dynamics. Specifically, the decreased intracellular sodium concentration within mature neurons results in higher peak voltages of action potentials.
Early in development, action potentials are relatively slow-rising and elongated. However, a developmental increase in sodium channel expression produces a more rapid depolarization, while a concurrent increase in potassium channels results in a shorter duration of action potentials.
By utilizing shorter action potentials, the cell can fire more rapidly and thus encode information more quickly. In addition to increased receptor expression, the localization of voltage-gated ion channels is essential to the efficient propagation of action potentials.
In myelinated axons, high-density clustering of voltage-gated channels to the nodes of Ranvier decreases the threshold for action potential initiation. Similarly, there is a clustering of voltage-gated sodium channels into lipid raft ‘micro-domains’ within unmyelinated axons.
The thinking is that this clustering optimizes action potential conduction and fidelity by lowering the number of channels required for propagation and by increasing the speed of conduction, compared to diffuse channel localization.
How does Action potential work?
A neuronal action potential has three main stages: depolarization, repolarization, and hyperpolarization. The initial depolarization is determined by the cell’s threshold voltage, the membrane potential at which voltage-gated sodium channels (Nav) open to allow an influx of sodium ions.
The flow of positive sodium ions into the cell leads to further depolarization of the membrane, thus opening more Nav in a positive-feedback loop. Depolarization in mature neurons lasts approximately 1 msec, at which time the Nav is inactivated and no longer able to flux ions.
Repolarization begins as voltage-gated potassium channels (Kv) open. Although Kv has approximately the same threshold voltage as Na, the kinetics of the potassium channel are much slower. Therefore, after approximately 1 msec, there is an opening of the slower Kv channels that is coincident with the inactivation of the faster Nav channels.
The flow of potassium ions out of the cell results in a decrease in membrane potential towards the cell’s resting voltage. When the membrane potential falls below the threshold, both the Nav and the Kv begin to close.
However, the Kv has slow kinetics and remains open slightly longer than needed to return the cell to resting membrane voltage. The brief dip in the membrane potential below the normal resting voltage is termed hyperpolarization.
Action potentials propagate a signal along the length of an axon differently in myelinated versus unmyelinated axons. Myelin, a lipid-rich membrane sheath surrounding some axons, insulates against the flow of ions. The myelin sheath is not continuous, but instead, there is axonal exposure at regularly spaced intervals termed the nodes of Ranvier.
Depolarizing current from an action potential travels very rapidly through the cytoplasm of axons, insulated by myelin until reaching the next node of Ranvier. At each node, the membrane depolarizes above the threshold voltage, and the influx of sodium ions again initiates the action potential through Nav.
This pattern of node-to-node propagation, saltatory conduction, can increase the conduction velocity by more than an order of magnitude over unmyelinated axons.
In unmyelinated axons, depolarization of the cell membrane must spread to the immediately adjacent region of the membrane, raising the potential passively until reaching the threshold voltage. Thus, the action potential propagates as a continuous wave of depolarization.
The initiation of a neuronal action potential usually occurs at the axon hillock, the most proximal segment of an axon. However, in sensory neurons, the action potential is initiated at the distal terminal of the axon and propagates toward the central nervous system. In these spike initiation zones, a 50-fold increase in Nav receptor density decreases input resistance, thus requiring less excitation to induce an action potential.