Neuroanatomy, neuron action potential (2023)


Neurons are electrically excitable and respond to input by generating electrical impulses that propagate through the cell and its axon as action potentials. These action potentials are generated and propagated across their plasma membranes by changes in the cationic gradient (mainly sodium and potassium). These action potentials eventually reach the axon terminal and cause depolarization of neighboring cells through synapses. This action is how these cells can interact with each other i.e. at synapses via synaptic transmission. Normally the inside of the cell is negative compared to its outside. This state is the resting membrane potential of about -60 mV. A neural action potential is generated when the negative internal potential reaches threshold (less negative). This change in membrane potential opens the voltage-gated cationic channel (sodium channel), leading to the process of depolarization and the generation of the neuronal action potential. Neural action potentials are crucial for the propagation of impulses along each nerve fiber, even over long distances. They are also crucial for communication between neurons via synapses. Disruption of this mechanism can have drastic effects, resulting in a lack of impulse generation and conduction, exemplified by various neurotoxins and demyelinating disorders.[1][2]

structure and function

The membrane potential of the neuron is generated by a difference in the concentration of charged ions. The lipid bilayer of the neuronal cell membrane acts as a capacitor, the transmembrane channels as resistors. This steady-state potential is critical to the neuron's physiological state, which is maintained by an uneven distribution of ions across the cell membrane and produced by ATP-dependent pumps—particularly sodium-potassium antiporters. These exchangers are responsible for pumping sodium from the cells into the extracellular space and potassium into the intracellular compartment. When open, different channels allow permeable ions to flow along their electrochemical gradients, altering the membrane potential. These channels are gated by second messengers, neurotransmitters, or voltage changes. Voltage-gated cationic channels are the main channels used in the generation and propagation of the neuronal action potential.

There are 100 billion neurons in the human brain and there are a quadrillion synapses in the human brain. Each neuron has an average of 1000 synapses that affect the electrical potential of the membrane. When the resting membrane potential (-60 mV) becomes less negative, it depolarizes. When it's more negative, it hyperpolarizes. Comparing the various ion movements, particularly the entry of sodium, the cell can have enough signals to reach the threshold potential and will reach this threshold by having enough positively charged ions entering the cell, i.e. H. end the polarity in a so-called depolarization. At normal body temperature, the equilibrium potential for sodium is +55 mV, for potassium -103 mV. There are three stages in action potential generation: (1) depolarization, change of membrane potential from -60 mV to +40 mV, mainly caused by sodium influx; (2) repolarization, a return to the membrane's resting potential, caused primarily by potassium efflux; and (3) post-hyperpolarization, a recovery from a slight repolarization overshoot.[3](see table below) As mentioned, stage 1 is controlled by increased membrane permeability to sodium. Accordingly, removal of extracellular sodium or inactivation of sodium channels prevents generation of action potentials.[4]Immediately after generating an action potential, the neuron cannot immediately generate another action potential; this is the absolute refractory period. At this moment, the sodium channels are inactivated and remain closed while the potassium channels are still open. This state is followed by the relative refractory period, during which the neuron is only allowed to generate an action potential with a much higher threshold. This opens when some of the sodium channels can be opened and many are still inactivated while some potassium channels are also still open. The duration of the refractory periods determines how quickly an action potential can be generated and propagated. Action potential propagation continues until termination at a synapse, where it can cause either the release of neurotransmitters or the conduction of ionic currents. The latter happens at electrical synapses, causing presynaptic and postsynaptic cells to connect and avoid using neurotransmitters.[5]However, neurotransmitters are the norm and are released at chemical synapses and neuromuscular junctions.[6]

Local currents generated by depolarization along a portion of the neuronal membrane, if sufficiently strong, can depolarize adjacent segments of the membrane to threshold, causing the action threshold to propagate along the membrane and along the neuron's axon. Crucial to the speed of this propagation is primarily the extent to which the initial local currents first propagate before producing further depolarizations. Factors affecting this rate include the electrical resistance of the membrane and the contents of the axon. Wider axons have lower internal resistance, and more voltage-gated membrane sodium channels also reduce membrane resistance. Higher internal resistance and lower membrane resistance contribute to slower action potential propagation. Because the body does not have enough space, to maximize the rate of propagation, instead of making large axons, the nervous system uses glial cells, particularly oligodendrocytes and Schwann cells, to wrap around axons and form myelin sheaths. These shells contribute to greater membrane resistance and patch areas where channels would otherwise leak. Still, the action potential can only propagate so far before more sodium channels are required to sustain the potential, creating gaps in the myelin sheath called Ranvier nodes. These nodes have high concentrations of these channels to restart the action potential down the axon, called saltatory conduction.[1]

Neuron action potential - see table in media below.

Clinical Significance

The rapid depolarization, or surge, of the neuronal action potential occurs as a result of the opening of the voltage-gated sodium channels. These channels are large transmembrane proteins with different subunits encoded by ten mammalian genes. Problems with these channels are collectively referred to as canalopathies. The canalopathies can affect any excitable tissue, including neurons, skeletal and cardiac muscle, resulting in several different diseases. The neurological channelopathies are more common in various muscle diseases and in the brain. Paramyotonia congenita results from mutations in the gene encoding the alpha 1 subunit of the sodium channel. Sodium channelopathies in the brain result in various forms of refractory epilepsy disorders.

There are a variety of neurotoxins that can block the action potential. One such deadly toxin is tetrodotoxin (TTX), which inhibits sodium channels.[7]The naturally occurring toxin is normally ingested orally by puffer fish, a part of Japanese cuisine, and its occurrence has spread beyond Southeast Asia to the Pacific and Mediterranean Seas, and this toxin has also been found in many other species. By binding to sodium channels and inactivating them, affected tissues are rendered immobile and desensitized. The onset/severity of symptoms arising from TTX depends on how much a person consumes, and patients may first present with tongue/lip paresthesia. This appearance is associated with or followed by headache/vomiting which can lead to muscle weakness and ataxia. Other symptoms include diarrhea, dizziness and loss of reflexes. Death can result from respiratory and/or cardiac failure. Of some clinical importance, however, TTX has some analgesic activity, which has been the subject of studies to treat pain, and a low dose can reduce heroin cravings. Unfortunately, TTX has no cure and is often fatal, with observation and supportive care being the only treatment. Respiratory support comes in the form of endotracheal intubation or mechanical ventilation to assist breathing. Early stages of intoxication can be treated with activated charcoal to adsorb the toxin before gastric absorption and gastric lavage to reduce symptom severity.[8]


Ciguatoxin is a potent sodium channel blocker that causes rapid onset of deafness, paresthesia, dysesthesia, and muscle paralysis. Ciguatoxins (CTX) are marine neurotoxins produced by dinoflagellates. CTX works by blocking the voltage-gated sodium channels. Humans are exposed to CTX through ingestion of carnivorous coral reef fish, including groupers, red snappers and barracuda, which feed on fish that have consumed the dinoflagellates.

Saxitoxin and its derivatives are known as paralytic shellfish toxins (PSTs). PSTs found in marine and freshwater environments among dinoflagellates act similarly to TTX and CTX, i.e. H. they bind to voltage-gated sodium channels and block the movement of nerve impulses and some degree of targeting to the potassium and calcium channels. Therefore, just like TTX, sodium cannot enter through the inactivated sodium channels, preventing membrane depolarization. Because of the similarity in their mechanism of action to TTX, PSTs have similar consequences. Severe exposure can result in severe hypotension and general paralysis, and death can result from respiratory failure/hypotension.[9][10]

To illustrate the importance of myelin in saline conduction, various demyelinating diseases that destroy myelin can have varying degrees of severity as they decrease the conduction velocity of action potentials.[11]Multiple sclerosis (MS) destroys oligodendrocytes, which help maintain the fatty layer of the myelin sheath, preventing the effective transmission of electrical signals. Eventually, this leads to complete loss of myelin and collapse of neuronal axons.[12]MS is common in white young adult women and can result in a wide range of physical, mental and psychiatric signs/symptoms such as: B. double vision, blindness, muscle weakness, speech problems, tremors, incontinence and dizziness. The diagnosis can be aided by an electrophoresis test for oligoclonal IgG bands in the cerebrospinal fluid, which is found in many MS patients.[13][14][15][16]


Figure 1: A. Two connected neurons. Neurons have a soma that contains the nucleus, an axon, and a dendritic tree. A single synapse (red circle) is formed at the point where the axon of one neuron (black) connects to the dendrite/part/axon of another (blue).(more...)


A neural action potential. The dashed line represents the threshold voltage. Used with permission from OpenStax under the Creative Commons Attribution 4.0 International License.

(Video) Neuron action potential - physiology


Neuron action potential - ion movements. Contributed by Forshing Lui MD

(Video) Action Potential in the Neuron



Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerves. 1952Stier Mathe Biol.1990;52(1-2):25-71; Discussion 5-23.[PubMed: 2185861]


Barnett MW, Larkman PM. The action potential.Praxis Neurol.June 2007;7(3):192-7.[PubMed: 17515599]


Grider MH, Jessu R, Kabir R.StatPearls [Internet].StatPearls publication; Treasure Island (FL): May 15, 2022. Physiology, action potential. [PubMed: 30844170]


Rutecki PA. Neuronal excitability: voltage-dependent currents and synaptic transmission.J Clin Neurophysiol.April 1992;9(2): 195-211.[PubMed: 1375602]


Zoidl G, Dermietzel R. In search of the electrical synapse: A glimpse into the future.cellular tissue.November 2002;310(2):137-42.[PubMed: 12397368]


Sheffler ZM, Reddy V, Pillarsetty LS.StatPearls [Internet].StatPearls publication; Treasure Island (FL): May 8, 2022. Physiology, Neurotransmitters. [PubMed: 30969716]


Jal S., Khora SS. A review of the origin and production of tetrodotoxin, a potent neurotoxin.J Appl Microbiol.Oct. 2015;119(4):907-16.[PubMed: 26178523]


Bane V, Lehane M, Dikshit M, O'Riordan A, Furey A. Tetrodotoxin: chemistry, toxicity, source, distribution and detection.Toxins (Basel).February 21, 2014;6(2):693-755.[PMC-free item: PMC3942760] [PubMed: 24566728]

(Video) 2-Minute Neuroscience: Action Potential


Diehl F, Ramos PB, Dos Santos JM, Barros DM, Yunes JS. Behavioral changes induced by repeated exposure to saxitoxin in drinking water.J Venom Anim Toxins Incl Trop Dis.2016;22:18.[PMC free article: PMC4869272] [PubMed: 27190499]


Cusick KD, Sayler GS. An overview of the marine neurotoxin saxitoxin: genetics, molecular targets, detection methods and ecological functions.Mar drug.Mar 27, 2013;11(4):991-1018.[PMC-free item: PMC3705384] [PubMed: 23535394]


Miller RH, Mi S. Dissection of demyelination.Nat Neurosci.November 2007;10(11): 1351-4.[PubMed: 17965654]


Compston A, Coles A. Multiple Sklerose.Lanzette.06.04.2002;359(9313): 1221-31.[PubMed: 11955556]


Compston A, Coles A. Multiple Sklerose.Lanzette.25. Oct. 2008;372(9648): 1502-17.[PubMed: 18970977]


Milo R, Kahana E. Multiple Sclerosis: Geoepidemiology, Genetics, and the Environment.Autoimmune Rev.2010 March;9(5): A387-94.[PubMed: 19932200]


Khan O, Williams MJ, Amezcua L, Javed A, Larsen KE, Smrtka JM. Multiple Sclerosis in U.S. Minorities: Insights into Clinical Practice.Neurol Clin Pract.April 2015;5(2):132-142.[PMC free article: PMC4404283] [PubMed: 26137421]


Link H, Huang YM. Oligoclonal bands in cerebrospinal fluid in multiple sclerosis: a methodology update and clinical utility.J Neuroimmunol.November 2006;180(1-2): 17-28.[PubMed: 16945427]


1. 2-Minute Neuroscience: The Neuron
(Neuroscientifically Challenged)
2. The Nervous System, Part 1: Crash Course Anatomy & Physiology #8
3. Neurology | Resting Membrane, Graded, Action Potentials
(Ninja Nerd)
4. 22. Neurons, Action Potential, & Optogenetics
(MIT OpenCourseWare)
5. Action Potential in Neurons, Animation.
(Alila Medical Media)
6. Action Potential in Neurons | Neurology | Dr Najeeb
(Dr. Najeeb Lectures)


Top Articles
Latest Posts
Article information

Author: Kerri Lueilwitz

Last Updated: 10/07/2023

Views: 6139

Rating: 4.7 / 5 (47 voted)

Reviews: 86% of readers found this page helpful

Author information

Name: Kerri Lueilwitz

Birthday: 1992-10-31

Address: Suite 878 3699 Chantelle Roads, Colebury, NC 68599

Phone: +6111989609516

Job: Chief Farming Manager

Hobby: Mycology, Stone skipping, Dowsing, Whittling, Taxidermy, Sand art, Roller skating

Introduction: My name is Kerri Lueilwitz, I am a courageous, gentle, quaint, thankful, outstanding, brave, vast person who loves writing and wants to share my knowledge and understanding with you.