Muscle I-b PDF

GENERAL CONSIDERATION OF STRIATED MUSCLE AND NEUROMUSCULAR JUNCTION -2- E-mail: [email protected]  MUSCLE ACTION POTENTIAL Membrane potential 2 3...

GENERAL CONSIDERATION OF STRIATED MUSCLE AND NEUROMUSCULAR JUNCTION -2- E-mail: [email protected]  MUSCLE ACTION POTENTIAL Membrane potential 2 3 1 4 5 STAGES OF ACTION POTENTIAL 1. RESTING Time (msec) 2. DEPOLARIZATION Resting membrane potential: -70 to -90 mV 3. REPOLARIZATION Duration of action potential: 1 to 5 ms 4. HYPERPOLARIZATION Velocity of conduction: 3 to 5 m/sec 5. RESTING  STAGES OF ACTION POTENTIAL 2 3 Membrane potential Na 3 Na 1 4 5 Na ATP 2 K Time (msec) K K 1. RESTING 2. DEPOLARIZATION intracellular 3. REPOLARIZATION Ca Ca 4. HYPERPOLARIZATION 5. RESTING extracellular  ROLE OF MOTOR NEURON Motor neuron is a single nerve cell extends from the brain or spinal cord to MUSCLE or gland. Skeletal muscle cells are electrically isolated from each other by endomysium. In order for skeletal muscle cells contract, each cell must be stimulated by motor neuron. NEUROMUSCULAR JUNCTION NEUROMUSCULAR JUNCTION  NEUROMUSCULAR JUNCTION Resting membrane potential: - 70 to - 90 mV The plus and minus signs indicate polarized condition called resting membrane potential. ARRIVAL OF ACTION POTENTIAL AT AXON TERMINAL When the action potential arrives at the axon terminal, the voltage change of the membrane opens voltage regulated calcium channels, allowing calcium ions to enter the axon terminal. FUSION OF SYNAPTIC VESICLES The calcium ions cause several synaptic vesicles to fuse with membrane of axon terminal. RELEASE OF ACETYLCHOLINE Acetylcholine (ACh) is extruded into the synapse by exocytosis.  ACETYLCHOLINE BINDS TO RECEPTOR SITES This binding causes the channels Acetylcholine binds to to open permitting an influx of receptor sites of chemically sodium ions and a small efflux regulated ion channels on of potassium ions. This ion the motor end plate. exchange causes a local depolarization of motor end plate. THE NICOTINIC ACETYLCHOLINE RECEPTOR ACTION POTENTIAL PROPAGATION  CALCIUM RELEASE FROM TERMINAL CISTERNAE The action potential causes the Calcium ions trigger a release of calcium ions from the contraction of muscle cell. terminal cisternae into cytosol. HOW? HOW? The action potential causes the release of calcium ions from the terminal cisternae into cytosol The action potential causes the release of calcium ions from the terminal cisternae into cytosol The propagation of the action potential into the T tubules depolarizes the triad region of the T tubules, activating L-type Ca2+ channels (pivotal role as the voltage sensor). The L-type Ca2+ channel is also often referred to as the DHP (dihydropyridine) receptor because it is inhibited by a class of antihypertensive and antiarrhythmic drugs known as dihydropyridines. Depolarization of the T-tubule membrane produces conformational changes in each of the four voltage-activated L-type Ca2+ channels of the tetrad, resulting in two major effects; First, the conformational changes Second, the conformational changes in allow Ca2+ to enter through the four the four L-type Ca2+channels induce a channel pores. conformational change in each of the four subunits of another channel—the Ca2+-release channel—that is located in the SR membrane. The action potential causes the release of calcium ions from the terminal cisternae into cytosol The Ca2+-release channel in the SR is also known as the ryanodine receptor because it is inhibited by a class of drugs that include the plant alkaloids ryanodine. After depolarization of the L-type Ca2+ channel on the T-tubule membrane and mechanical activation of the Ca2+-release channel in the SR, Ca2+ stored in the SR rapidly leaves through the Ca2+-release channel. The resultant rapid increase in [Ca2+]i activates troponin C, initiating formation of cross- bridges between myofilaments. Excitation-contraction coupling (ECC) in skeletal muscle thus includes the entire process, beginning with the depolarization of the T-tubule membrane to the initiation of the cross-bridge cycle of contraction. EC coupling in skeletal muscle primarily involves direct mechanical coupling between the L-type Ca2+channel in the T-tubule membrane and the Ca2+-release channel of the SR, a second mechanism, Intracellular Ca2+ can directly activate the Ca2+-release channel in the SR—a process known as Ca2+-induced Ca2+ release (CICR).  BREAKDOWN OF ACETYLCHOLINE After a brief period acetylcoline Acetylcholine is than broken diffuses away from its receptor down by the enzyme site and the ion channel closes. acetylcolineesterase.  MYASTHENIA GRAVIS 1 in every 20,000 persons autoimmune disease Antibodies that attack the acetylcholine receptors MYASTHENIA GRAVIS Curare Curare is the name given to various highly toxic substances used by certain indian tribes in South America to poison their hunting arrows. Curare is also the name given to the plants that produce the toxic substances. Curare paste was applied to arrowheads and used to kill prey when hunting. Animals struck by the poisoned arrow heads are unable to run away and die within minutes. Curare binds directly to nicotinic receptors on the postsynaptic membrane of the neuromuscular junction, which prevents the binding of ACh and depolarization of the motor endplate, leading to muscle paralysis. Curare repeatedly binds and dissociates from the receptor, so it can be displaced by ACh and its effects reversed. Botox Botox is a drug made from a toxin produced by the bacterium Clostridium botulinum. It's the same toxin that causes a life-threatening type of food poisoning called botulism. Doctors use it in small doses to treat health problems, including Temporary smoothing of facial wrinkles and improving your appearance Severe underarm sweating Cervical dystonia - a neurological disorder that causes severe neck and shoulder muscle contractions Blepharospasm - uncontrollable blinking Strabismus - misaligned eyes Chronic migraine Overactive bladder  Botox Botulinum toxin, the most potent of the neurotoxins, produces paralysis by blocking presynaptic release of the neurotransmitter (acetylcholine) at the neuromuscular junction, with reversible chemical denervation of the muscle fibre, thereby inducing partial paralysis and atrophy Botox injections work by weakening or paralyzing certain muscles or by blocking certain nerves. SUMMARY Each skeletal muscle cell is individually stimulated by a motor neuron. The neuromuscular junction is the place where the terminal portion of a motor neuron meets a muscle cell membrane, separated by a synaptic cleft. An action potential arriving at the axon terminal brings about the release of acetylcholine, which leads to depolarization of the motor end plate. Depolarization of the motor end plate triggers an action potential that propagates along the sarcolemma and down to T tubules. This action potential causes the release of calcium ions from the terminal cisterna into cytosol, triggering contraction of the muscle cell. https://www.youtube.com/watch?v=CLS84OoHJnQ