A condition where excessive magnesium (Mg) blocks Ca²⁺ influx, resulting in decreased neurotransmitter exocytosis and impaired neuromuscular junction (NMJ) transmission.
The acetylcholine receptor is a mixed-cation channel that allows the simultaneous flow of Na+ and K+ ions.
End Plate Potentials (EPP) are local depolarizations that occur at the motor end plate in response to acetylcholine binding, which do not propagate like action potentials.
Flaccid paralysis is a condition characterized by insufficient or absent end-plate potential (EPP) due to the blockade of ACh receptors by non-depolarizing neuromuscular blockers.
A condition characterized by insufficient magnesium (Mg) competing at Ca²⁺ channels, leading to increased neurotransmitter exocytosis and enhanced neuromuscular junction (NMJ) transmission.
Acetylcholine (Ach) is released from the motoneuron and binds to receptors on the motor end-plate, leading to the generation of the end-plate potential.
Magnesium regulates neurotransmitter release by blocking some Ca²⁺ channels at the NMJ, influencing the amount of neurotransmitter exocytosis.
Acetylcholinesterase rapidly degrades Acetylcholine into choline and acetate, facilitating its removal from the synaptic cleft.
Acetylcholine, Norepinephrine, and GABA.
A sufficient dose of Curare can cause eventual death by asphyxiation due to paralysis of the diaphragm.
Diagnosis of Myasthenia Gravis involves detecting serum antibodies or testing for response to anti-cholinesterases.
Organophosphate pesticides and many nerve gases are classified as anti-cholinesterases.
Physiological means for modulation include changes in ion concentrations, neurotransmitter levels, and receptor sensitivity that can enhance or inhibit neuromuscular transmission.
Depolarizing paralysis, which requires respiratory support.
Excitation-secretion coupling in the NMJ refers to the process by which an action potential in a motor neuron leads to the release of acetylcholine at the neuromuscular junction, ultimately resulting in muscle contraction.
Anti-cholinesterases are compounds that inhibit acetylcholinesterase, allowing acetylcholine (ACh) to accumulate in the synaptic cleft.
AChE Inhibitors slow down the breakdown of acetylcholine, leading to increased levels of ACh in the synaptic cleft.
Pharmacological agents such as neuromuscular blockers, anti-cholinesterases, and certain anesthetics can either enhance or inhibit neuromuscular transmission.
The end-plate potential (EPP) is a depolarizing graded potential that occurs at the motor end-plate due to the opening of acetylcholine receptors.
The binding of Acetylcholine to the receptor is very brief, leading to its rapid degradation by Acetylcholinesterase.
The MOTOR END PLATE is the portion of the sarcolemma directly across from the synaptic terminal, similar to membranes in the soma and dendrites of neurons, and contains chemically-gated ion channels that bind acetylcholine, capable of generating End Plate Potentials (EPP) but not action potentials.
Non-depolarizing blockers are antagonists that competitively bind to ACh receptors, preventing ion channels from opening, leading to insufficient or absent end-plate potential (EPP) and resulting in flaccid paralysis. An example is Curare (D-Tubocurarine).
Pathophysiological states such as myasthenia gravis, electrolyte imbalances, and certain neurological disorders can impair neuromuscular transmission, leading to muscle weakness.
The EPP is a graded potential.
The release of acetylcholine at the neuromuscular junction is initiated by an action potential from the motoneuron.
Myasthenia Gravis is an autoimmune disorder caused by antibodies against acetylcholine (ACh) receptors, leading to diminished function and numbers of these receptors.
High doses cause fibrillations, muscle fasciculations, and eventually lead to depolarizing muscular paralysis.
Voltage-gated calcium channels are crucial for the influx of calcium ions, which triggers the release of acetylcholine at the neuromuscular junction.
A neurotoxin that forms pores in the lipid membranes of the presynaptic terminal, inducing Ca2+ flow and enhancing neurotransmitter release.
Curare functions by competitively and reversibly inhibiting the nicotinic acetylcholine receptor, leading to weakness of skeletal muscles.
Tetanus toxin (TeNT) cleaves SNAREs involved in synaptic exocytosis of GABA primarily in inhibitory interneurons to skeletal muscles, resulting in muscle spasms and eventual spastic paralysis.
Substances that bind to and activate acetylcholine receptors, mimicking the action of acetylcholine.
Botulism Flaccid Paralysis is caused by the botulinum toxin, which inhibits the release of acetylcholine at the neuromuscular junction, leading to muscle weakness and paralysis.
The EPP magnitude depends on the amount and duration of acetylcholine (ACh) at the motor end plate.
Curare is the common name for plant extract alkaloids originating from Central and South America that inhibit the nicotinic acetylcholine receptor at the neuromuscular junction.
Common symptoms include muscular weakness, ptosis, diplopia, blurred vision, dysarthria, and dysphagia.
Prolonged depolarization leads to paralysis from the inactivation of voltage-gated sodium channels.
Autoimmune destruction of ACh receptors reduces the number of available receptors, leading to decreased EPP magnitude and impaired muscle contraction.
Excitation-secretion coupling is the process by which an action potential in a motor neuron leads to the release of neurotransmitters at the neuromuscular junction, ultimately resulting in muscle contraction.
Choline is returned to the presynaptic knob where it is recycled and reformed with acetyl-CoA into Acetylcholine.
Botulism toxin (BoNT) cleaves SNAREs involved in synaptic exocytosis of acetylcholine (Ach) primarily in skeletal muscle motorneurons, resulting in flaccid muscle paralysis and autonomic nervous system (ANS) cholinergic dysfunction.
Neostigmine and pyridostigmine are examples of anti-cholinesterase therapeutic drugs.
Voltage-gated Na+ channels are crucial for the propagation of action potentials in the sarcolemma; their inactivation during prolonged depolarization leads to paralysis.
Muscle spasms, intense-cramping pain, and generalized nervous system excitation.
Acetylcholinesterase is present in the post-synaptic folds at the synaptic cleft.
Treatment with anti-cholinesterases, such as Mestinon (pyridostigmine), leads to motor improvement in patients with Myasthenia Gravis.
Substances that bind to acetylcholine receptors but do not activate them, blocking the action of acetylcholine.
Tetanus Spastic Paralysis is caused by tetanospasmin, a toxin that blocks inhibitory neurotransmitter release, resulting in continuous muscle contraction and spasms.
The EPP is the postsynaptic potential induced at the neuromuscular junction by the opening of the nicotinic acetylcholine receptor, which partially depolarizes the motor end-plate membrane and can initiate an action potential in the muscle sarcolemma.
A process that occurs during neuromuscular transmission modulation, affecting the excitability of neurons.
End-plate potentials are graded potentials that occur at the neuromuscular junction, while sarcolemma action potentials are all-or-nothing responses that propagate along the muscle fiber membrane, leading to muscle contraction.
Low doses cause lacrimation, salivation, bradycardia, sweating, vomiting, and diarrhea due to nicotinic and muscarinic effects via the autonomic nervous system.
The amount of ACh released directly influences the magnitude of the end-plate potential (EPP); more ACh leads to a larger EPP.
End-plate potentials (EPPs) are localized depolarizations of the muscle membrane at the neuromuscular junction, caused by the binding of acetylcholine to receptors, which can lead to muscle action potentials.
The SARCOLEMMA is the plasma membrane of a muscle cell or fiber, electrically similar to axonal plasma membranes, containing voltage-gated Na+ and K+ channels, and capable of initiating and propagating self-regenerating action potentials.
Depolarizing blockers act as agonists that cause prolonged activation of ACh receptors, leading to continuous depolarization of the endplate for more than 2-3 minutes, resulting in inactivation of voltage-gated Na+ channels and ultimately causing involuntary contractions followed by depolarization-induced paralysis. An example is Succinylcholine.
Predicted outcomes of modulation can include improved muscle function, increased muscle fatigue, or exacerbation of paralysis, depending on the nature of the modulation.
In Myasthenia Gravis, the EPP decreases despite normal release of acetylcholine.
Action potentials in the context of the sarcolemma are self-regenerating electrical signals that can initiate and propagate along the muscle fiber, unlike the EPPs at the motor end plate.
Depolarization-induced paralysis occurs after prolonged activation of ACh receptors by depolarizing blockers, leading to continuous depolarization and inactivation of voltage-gated Na+ channels, resulting in muscle paralysis.
