Neuroanatomy, neuron action potential (2023)

introduction

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]

references

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(Video) 2-Minute Neuroscience: Action Potential

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