NEUROMUSCULAR JUNCTION

• The neuromuscular junction (NMJ) is where nerve signals meet muscle fibers.
• When an action potential reaches the motor nerve terminal, it triggers calcium influx, leading to the release of acetylcholine.
• Acetylcholine ensures signal termination, maintaining precise neuromuscular control.
• neuromuscular junction (NMJ) is a critical site where nerve signals are transmitted to skeletal muscle fibers, facilitating muscle contraction.
• motor end plate is a specialized region on the muscle fiber membrane. It features a high concentration of acetylcholine receptors, allowing for efficient communication between the motor neuron and the muscle fiber.
• voltage-gated calcium channels open, leading to an influx of calcium ions. This influx triggers the release of acetylcholine from synaptic vesicles into the synaptic cleft.
• Acetylcholine binds to its receptors on the motor end plate, initiating a depolarization of the muscle membrane. This depolarization propagates along the muscle fiber, eventually leading to muscle contraction.
• The role of acetylcholinesterase is crucial in terminating the signal by breaking down acetylcholine, preventing continuous stimulation and ensuring precise control of muscle activity at the
• Acetylcholine secretion at nerve terminals involves calcium influx triggering vesicle fusion. This releases acetylcholine into the synaptic cleft, facilitating its binding to motor end plate receptors and initiating muscle depolarization for contraction.
• When an action potential reaches the nerve terminal, voltage-gated calcium channels open, allowing an influx of calcium ions.
• This calcium influx triggers the fusion of acetylcholine-containing vesicles with the nerve terminal membrane, releasing acetylcholine into the synaptic cleft.
• exocytosis, enables acetylcholine to bind to its receptors on the motor end plate of the muscle fiber.
• Acetylcholine binding to postsynaptic receptors on muscle fiber membranes triggers the opening of ion channels, specifically nicotinic acetylcholine receptors. This leads to an influx of sodium ions, causing depolarization and ultimately initiating muscle contraction.
• By breaking down acetylcholine, acetylcholinesterase prevents the continuous stimulation of the postsynaptic membrane and allows for the proper functioning of the neural circuitry.
• The sudden rising of sodium ions into the muscle fiber when the acetylcholine-gated channels open causes the electrical potential inside the fiber at the original area of the end plate to increase in the positive direction as much as 50 to 75 millivolts, creating a local potential called the end plate potential.
• Stimulation of the nerve fiber at rates less than 100 times per second for several minutes frequently diminishes the number of acetylcholine vesicles so much that impulses fail to pass into the muscle fiber. This situation is called fatigue of the neuromuscular junction, and it's the same effect that causes fatigue of synapses in the central nervous system when the synapses are overexcited.
• Safety factor for Transmission at the Neuromuscular Junction

  Refers to the degree to which the neuromuscular transmission is reliable and ensures the successful transmission of the signal from the motor neuron to the muscle fiber.
• safety factor is a measure of the overcapacity or reserve in the neuromuscular system, beyond what is required for normal transmission. It serves as a built-in protective mechanism to ensure that even under less than optimal conditions, such as in fatigue, there is still sufficient transmission of the neural signal to initiate muscle contraction.’
• Small vesicles, 40 nanometers in size, are formed by the Golgi apparatus in the motor neuron cell body in the spinal cord.
• Acetylcholine, synthesized in the nerve fiber terminal's cytosol,
• An action potential at the nerve terminal opens calcium channels, increasing calcium ion concentration and fusion of acetylcholine vesicles with the terminal membrane. This
• Drugs That Stimulate the Muscle Fiber by Acetylcholine- Like Action.

  Methacholine

  carbachol

  nicotine
• Methacholine, carbachol, and nicotine

  Unlike acetylcholine, these drugs resist cholinesterase destruction, leading to prolonged action, creating localized depolarization at motor end plates, inducing muscle spasms.
• Methacholine- used in medical test for lung function
• Carbachol- used in ophthalmology to treat certain eye conditions, such as glaucoma and intraocular hypertension.
• • Nicotine it comes from tobacco plants. Known for smoking but it is also used for patches and gums that can help people quit smoking.
• These substances, like nicotine, carbachol, and methacholine, can influence how muscles work by affecting signals and receptors. While they don't directly cause "ion loss," they impact the way ions move in and out of muscle cells, influencing muscle activity.
• every time the muscle fiber recovers from a previous contraction, these depolarized areas, by the means of leaking ions, initiate a new action potential, thereby causing a state of muscle spasm.
• • Neostigmine
  • Physostigmine
  • Diisopropyl fluorophosphate.

  
  

  These drugs are notable for inhibiting acetylcholinesterase, preventing acetylcholine breakdown.
• Neostigmine and physostigmine offer several hours of inactivation, while diisopropyl fluorophosphate, a potent nerve gas poison, has a prolonged effect lasting weeks.
• Neostigmine and physostigmine are primarily used in medical settings to address conditions related to neuromuscular function. They are often employed to reverse the effects of muscle relaxants used during surgery or to manage conditions associated with muscle weakness, such as myasthenia gravis.
• Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction, where nerves and muscles meet. In this condition, the immune system mistakenly targets and attacks receptors for acetylcholine, a neurotransmitter responsible for muscle contractions. As a result, communication between nerves and muscles is impaired, leading to muscle weakness and fatigue.
• Diisopropyl fluorophosphate (DFP) is not used for medical purposes due to its extreme toxicity. It is a potent cholinesterase inhibitor, affecting the enzyme that breaks down acetylcholine in the nervous system. Due to its highly toxic nature, its use is strictly controlled, and it is not utilized in mainstream medical treatments.
• D-tubocurarine, hinder nerve impulses from reaching muscles by blocking acetylcholine action on muscle fiber receptors. This prevents an adequate increase in membrane permeability, inhibiting the initiation of an action potential.
• D-tubocurarine is a drug that was once used during surgery to make muscles relax. It is a medicine used during surgery to relax muscles, making it easier for doctors to perform procedures.
• Myasthenia gravis, a rare disease, causes muscle paralysis due to insufficient nerve fiber transmission. Patients develop antibodies that attack acetylcholine receptors, making it an autoimmune disease.
• Myasthenia gravis can be alleviated with neostigmine or other anticholinesterase drugs, allowing larger amounts of acetylcholine to accumulate in synaptic space.
• Resting membrane potential: about −80 to −90 milli- volts in skeletal fibers—the same as in large myelinated nerve fibers.
• Duration of action potential: 1 to 5 milliseconds in skeletal muscle—about five times as long as in large myelinated nerves.
• The size and structure of the muscle fiber make it challenging for these signals to penetrate deeply. Yet to cause maximum muscle contraction, current must penetrate deeply into the muscle fiber to the vicinity of the separate myo- fibrils.