Introduction The neuron, or nerve cell, is the basic structural and functional unit of the human nervous system. It is an electrically excitable cell whose function is to transmit information and signals across the body, which it does through electrical as well as chemical signals. Neurotransmission, i.e. the process of communication of information via the neurons, is typically understood as the transmission of nerve impulses across a synapse, which is from one neuron to another. However, before the impulse can pass from one axon ending to the dendrites of another cell across a synapse, the impulse needs to first travel through the length of the pre-synaptic neuron itself. While neurotransmission across synapses is typically chemical in nature, where neurotransmitters are released and diffused to the receptors of another neuron which they bind and activate, the neuronal transmission that takes place within the neuron is electrical in nature. This internal process within the nerve cell can be understood as different and distinct from that of chemical neurotransmission.
To understand the electrical transmission within the neuron, it is first important to understand two things: the first is the basic structure of the neuron, and the second is the nature of an electrical change. Structure of the Neuron In brief, the neuron or nerve cell consists of dendrites, a soma or cell body, an axon, and axon terminals. The dendrites have spines, which are smaller protrusions, and the main function of the dendrites is to receive synaptic signals from other neurons that they are in contact with. The soma is basically the cell body, and contains the nucleus which is the life- force of the nerve cell. Emerging out from the soma is the axon hillock, which connects the soma to the axon, and contains a high concentration of voltage-activated sodium channels. This is the zone considered to be the spike initiation zone for action potentials, which play a crucial part in electrical transmission within the neuron. Multiple signals received by the various dendrites and then transmitted by the soma all converge here, from where they travel electrically through the axon, which is the next connected segment. The axon is myelinated for insulation, and this myelin layer is made of glial cells, which are either Schwann cells or oligodendrocytes, with the former found in the peripheral and the latter in the central nervous system. There are, however, unmyelinated patches of cell membrane along the length of the axon placed at regular intervals, known as the nodes of Ranvier, which act as mini axon hillocks, and work to boost signal transmission and prevent significant signal decay. Towards the end of the axon are present the axon terminals, where the myelinated insulation is lost and the axon ending branches out. These axon endings contain pockets of neurotransmitters enclosed within what are called synaptic vesicles, ready to be released into the synapse for the next neuron upon stimulation. At this point, the axon terminals become pre-synaptic, and the neuron that receives the neurotransmitter becomes the post-synaptic neuron. Furthermore, this is the point where electrical transmission within the neuron stops and chemical neurotransmission across synapses begins once again. Structure of a Neuron (next page)
Nature of an Electrical Charge The flow of current through a conductor is caused by the movement of electrons, which are negatively charged particles, from a point where they are in a high concentration to a point where they are in low concentration. The difference between the number of electrons at these two different points is what is known as voltage, measured in volts. The amount of voltage difference between the two points plays an effect on current flow, making it more rapid. Neuronal transmission within the neuron is electrical in nature, and follows these same principles in the transmission of impulses from one end of the nerve cell to the other. Resting Potential The inside of the neuron contains a large number of negative ions and the outside with an equally large number of positive ions. These two kinds of ions are separated by the cell membrane, which prevents the entry of positive ions into the neuron, as well as the exit of negative ions from the neuron. Owing the polarity caused by the presence of oppositely charged ions on either side of the cell membrane, this state of the nerve cell is termed as the polarized condition. The difference between the positive outside of the membrane and the negative inside of the cell is what is known as resting potential, and usually stands at a value of -70mV.
Action Potential When a nerve cell receives a synaptic message from a neighbouring cell, and electric charge is sparked off in the axon, starting at the axon hillock. This is where the role of the nerve fibres as electrical conductors comes in. the electrical impulse generated within the neuron that travels along the length of the axon to finally trigger the next synaptic chemical neurotransmission, is called the action potential. This action potential travels like a wave along the nerve fibres this means that the action potential generated at one point creates another gradient of voltage between the active point and the point adjacent to it that is in resting potential. Thus, the movement of the action potential along the axon is like a wave of depolarization that moves through its length point by point.
How does the action potential work to depolarize the nerve cell? This is achievable because of the afore-mentioned presence of positive and negative ions that exist on either side of the cell membrane. A voltage difference exists, which makes the flow of current a potent possibility. However, this flow of current cannot take place at other times owing to the membrane that is blocking the flow of ions into and out of the nerve cell. However, this barrier also contains a series ion channels at every point that can be stimulated to open and close, thus letting ions in and out. When the post-synaptic nerve cell receives a chemically neurotransmitter from the pre-synaptic nerve cell, it accordingly stimulates the opening of these ion channels. The opening of the ion channels allows the positively charged ions to flow into the axon while the negatively charged ions to move outwards, thus creating a depolarized state. It has already been stated that action potential works by creating a gradient in the neighbouring point, thus allowing the electrical charge to move like a wave along the length of the axon. However, how is this maintained if the very first point in the cell is depolarized by the opening of the ion channels? This is answered by the mechanism of the two kinds if ion channels that exist along the axonal membrane the sodium ion channels and the potassium ion channels. Sodium ions (+Na) are positively charged ions that are found in the outside of the cell membrane in greater concentration than inside it. Potassium ions (+K) are also positively charged ions, but are usually found inside the axonal membrane, though in lower concentration than that of the negative ions that exist inside it. This means that a large number of sodium ions are found outside the cell membrane, which is the area that has a positive charge. A small number of potassium ions are found inside the cell membrane, which has a predominantly negative charge. When action potential is generated, the first ion channels to open are the sodium channels. The opening of the ion channels leads to a rushing in of sodium ions to the negatively charged inside of the axonal membrane. 1 This leads to rapid depolarization, as the charges become balanced on the inside as well as the outside due to the entry of the positively
1 As mentioned in the section on Nature of an Electrical Charge, electrical charge works along the lines of the movement of negatively charged ions, i.e. electrons, from an area of higher to lower concentration; however, in the neuron since it is the positive ion, i.e. the sodium ion, that is initiating the current flow (by the opening of the ion channel), current flow is indicated as positive to negative. In actuality there are ions that are moving in both directions. charged sodium ions into the negatively charged axon. The rapid flow of current leads to a sudden switch in voltage what was -70mV before the flow of current (resting potential) increases by about 100mV, leading to a current voltage of +30mV. The transmembrane voltage is thus changed from negative to positive and this, in turn, leads to the opening of the next set of ion channels, i.e. the potassium ion channels.
Just as rapidly as the sodium channels flowed into the axonal membrane, the potassium channels flow out of it. This in turn causes the voltage within the membrane to switch back to its original negative value, and pass on the gradient to the neighbouring point in the axonal membrane. Nature of Resting Potential The mechanism of resting potential has been discussed in an earlier section; however, an understanding of its nature and maintenance is important to gaining a clear understanding of the concept of resting potential in a neuron.
The axonal membrane contains an interesting mechanism of ion pumps that contribute towards the maintenance of resting potential in the absence of stimulation. These ion pumps include sodium pumps as well as potassium pumps. As has already been discussed, it is clear that the concentration of positively charged sodium ions is much higher outside the axonal membrane. The sodium pump is actively at work in order to expel any excessive sodium ions during resting potential. Similarly, the potassium pump is also actively at work in order to contain a certain number of potassium ions during resting potential. It is important to note that only a certain number of potassium ions are worked to be contained inside the membrane, i.e. a small enough number that their collective charge does not upset the voltage difference cause by the higher positive charge outside the membrane. It is also these pumps that are work to bring the neuron back to its initial state of depolarization, when the exchange of sodium and potassium ions takes place during transmission of nerve impulse. In actuality, a very few number of sodium and potassium ions make the exchange during this process, and this number is not enough to significantly modify the positive and negative charges of the outside and inside of the membrane respectively. However, the ion pumps are still at work in expelling sodium ions and re-containing potassium ions, in order to prevent an accumulation of either kind in the wrong space which would cause a consequent depolarization of the neuron.
Another mechanism adopted by the neuron in order to maintain the voltage difference, and thus the resting potential, is by the size of the ions that it contains. A number of negatively charged ions contained within the membrane are of too large a size to be able to pass through the pores of the membrane. Thus, this restricts the flow of electrons from an area of higher to lower concentration, i.e. from inside the membrane to the outside of it, helping maintain the polarized state of the neuron. Nature of the Action Potential The mechanism of the action potential has already been discussed; however, action potential further involves a few more characteristics that become important in understanding its functioning. Impulses can travel at different speeds along an axon however, this is NOT regulated by the intensity of electrical impulse that is generated. The action potential follows an all-or-none law. This means that if, and only if, a certain threshold of stimulus intensity is achieved, will and electrical current be initiated. Stronger stimuli do not result in larger or faster nerve impulses. How this works is, when a certain threshold of intensity is achieved, then the nerve cell itself generates the current, i.e. the action potential, in the manner discussed in the earlier section. Since the generation of current is internal to the neuron, the generation of the current in terms of the speed of the impulse is independent of the stimulus. If the critical threshold is not reached, then no action potential is generated. If the critical threshold is reached, then action potential is generated. If intensity is higher than the critical threshold, action potential is, of course, generated, but the speed or nature of the impulse does not differ at all from an impulse generated by exactly meeting the critical threshold. Thus, action potential is based on an all-or-none law hitting threshold results in complete generation of current; not meeting it evokes no response, not even a weak one. The speed of impulse is dictated by the diameter and myelination of the neuron that is being stimulated, and not on the nature or intensity of the stimulus.
Since action potential is self-propagating in nature, it electrotonically conducts itself in a circular motion to every part of the axon, transversing it in both direction. This is the process of conduction in unmyelinated cells; in myelinated cells, however, the action potential is of a different nature. There, the depolarized state jumps from one node of Ranvier to the next one. Thicker axons are the ones that are myelinated, and hence these are the axons in which such conduction happens. This method of conduction is also faster. Thus, axons with a larger diameter, i.e. myelinated axons, usually feature a faster conduction velocity for impulse within the neuron. The conduction is slower in axons with smaller diameters, i.e. unmyelinated or lesser myelinated axons.
The conduction on unmyelinated axons, as mentioned, is electrotonically conducted, i.e. the depolarization is propagated in circular waves from the site of generation of the action potential. This technically concludes that conduction of impulse can happen multi- directionally within the axon, and this is called antidromic conduction. However, chemical neurotransmission, i.e. synaptic transmission, only happens in one direction. Therefore, when the antidromic depolarized waves meet the site of the first synapse, i.e. the direction of the dendrites of the neuron in which the action potential was generated itself, these waves wane out. This results in the commonly understood pattern of transmission from receptors to synaptic junctions to synaptic terminals, and from there to the next neuron. This type of conduction is termed as orthodromic conduction. During the generation of action potential, it has been discussed how sodium ions are let into the membrane via sodium channels. This is also due to the increased permeability of the membrane towards the entry of sodium ions. Once the action potential has passed on, the permeability of the membrane rapidly declines. This is followed by a temporary increase in the permeability of the membrane towards potassium ions (those that were contained in the membrane during resting potential but travel outwards during action potential). This becomes the reason for a temporary period of hyperpolarization that follows the depolarization. Furthermore, the passing of an action potential is followed by an absolute refractory period. Due to the increased permeability towards sodium ions, the neuron will not respond to new activation temporarily. Furthermore, for several milliseconds after the end of the absolute refractory period, it becomes difficult for a new action potential to be generated in the neuron. This is, as mentioned, due to the hyperpolarization that follows.
Finally, the role of sodium and potassium pumps has already been mentioned in an earlier section. As discussed, during the exchange of sodium and potassium ions that takes place during generation of action potentials, very few ions are actually involved in a single instance, thus no significant difference is brought about to the overall charge of the inside and outside of the membrane. However, prolonged and repeated trains in generation of action potential can result in measurable changes in ionic concentration. Thus, the sodium and potassium pumps work to compensate for the leakages that take place through the ionic channels. The ratio is 3:2 for every three sodium ions that are expelled, two potassium ions are taken in. References: Foxit Software. (2014, June 26). Brain Campaign. Retrieved from Brain Campaign Web site: http://psych.hanover.edu/Krantz/neurotut.html Leukel, F. (1976). Introduction to Physiological Psychology. C.V. Mosby Company. Oja, S. S., & Saransaari, P. (n.d.). Neurons, Action Potentials, and Synapses. Encyclopedia of Life Support Systems.