Muscle - PDF

Muscle Dr. Shimaa Magdy  Muscle is a tissue that shortens and develops tension leading to movement. Types of muscle: 1-Striated muscles (skeletal & cardiac) 2- Smooth muscles  PHYSIOLOGY OF SKELETAL MUSCLES  40% of the body is skeletal muscles (400 skeletal muscles).  When contra...

Muscle Dr. Shimaa Magdy  Muscle is a tissue that shortens and develops tension leading to movement. Types of muscle: 1-Striated muscles (skeletal & cardiac) 2- Smooth muscles  PHYSIOLOGY OF SKELETAL MUSCLES  40% of the body is skeletal muscles (400 skeletal muscles).  When contract, they move the body.  They are made of many muscle fibers arranged in parallel bundles.  Each muscle fiber is a single cell, has sarcolemma, many nuclei and many parallel myofibrils.  Each myofibril contains thick filaments (myosin) and thin filaments (actin). The sarcomere:  It is the functional unit of the muscle.  It extends between two transverse protein sheets called Z lines.  Contains the thick filaments myosin in the middle of the sarcomere.  Contains the thin filaments actin which are arranged on both sides of the sarcromere with one end attached to the Z line and the other overlap with the thick filament myosin.  Titin (elastic protein) attaches the thick filaments to Z line.  A band : myosin & actin I band : actin. H zone : myosin (lighter in color) The sarco-tubular system 1- T-tubules: It is an invagination of muscle fiber membrane at the junction of dark (A) and light (I) bands. It transmits action potential from the surface of muscle fiber to inside the fiber. 2- The sacrcoplasmic reticulum (SR) It extends longitudinally between the T-tubules parallel to muscle fibers, It is a site of storage of Ca2+. The ends of SR expands and form the terminal cisternae that are in contact with T-tubules. Thick filaments (myosin)  Each myosin molecule is made up of 2 heavy chains and 4 light chains.  The two heavy chains form a helix; their terminal portions with the 4 light chains form 2 arms and globular heads called cross bridges.  The myosin head contains.  -Actin binding site.  - ATP binding site.  -ATP pase activity that hydrolyses ATP.  Thin filaments: Consists of three muscle proteins Actin Tropomyosin Troponin 1- Actin molecule Is arranged in double helix and has active sites that can bind with myosin cross bridges. 2-Tropomyosin molecules Form strands that cover active sites on actin molecules during rest.  3- Troponin Globular proteins Formed of three subunits Troponin I: has affinity to actin Troponin T: has affinity to tropomyosin Troponin C: has affinity to Ca2+ Troponin attaches tropomyosin strands to actin NEUROMUSCULAR TRANSMISSION  It is the transmission of action potential from alpha motor nerve to the muscle along the neuromuscular junction. The neuromuscular junction:  It is the area between the ending of motor nerve and skeletal muscle fiber.  The motor nerve as it comes near the muscle, it branches to terminals which ends by (terminal knobs ) end feet that contain the acetylcholine vesicles.  The terminal knob fits into a depression in the membrane of the muscle fiber called motor end plate (MEP)..  The motor end plate membrane is thickened and folded and contains acetylcholine receptors.  The space between the nerve and the MEP is called synaptic cleft which contains extracellular fluid (ECF) and acetylcholine esterase enzyme. STEPS OF NEUROMUSCULAR TRANSMISSION : 1-Arrival of action potential (AP)  As the action potential reaches the ending of the motor nerve, the permeability of the membrane of the nerve terminal to Ca2+ increases and Ca2+ enter the nerve endings. This causes rupture of acetylcholine vesicles and release of acetylcholine. 2-Postsynaptic response:  Acetylcholine diffuses and binds to its receptors on the MEP. This leads to an increase in the permeability of the MEP membrane to Na+, Na+ influx will cause depolarization of the membrane of MEP called end plate potential (EPP). 3- The end plate potential (EPP) EPP is graded, non propagated response. EPP depolarizes the adjacent muscle membrane to firing level and produces AP on both sides which are conducted on both directions along the muscle fiber. Muscle action potential initiates muscle (contraction). 4- Acetylcholine degradation: Acetylcholine dissociates from the receptors and is hydrolysed by choline esterase in the synaptic cleft.  Properties of neuromuscular transmission: (NMT) 1- Unidirectional: from nerve to muscle 2- Delay: There is a delay about 0.5msec. This time is needed for acetylcholine release, change in permeability of muscle membrane to ions, influx of Na+ and building of EPP. 3-Fatigue: Repeated stimulation and exhaustion of synaptic vesicles (acetylcholine exhaustion). 4- Effect of ions: Increase of Ca2+ increases acetylcholine release. Increase of Mg++ decreases acetylcholine release. 5- Effects of drugs a- Drugs that stimulate NMT Drugs that have acetylcholine like actions e.g.metacholine, carbacol & nicotine in small dose. Drugs that inactivate choline- esterase e.g neostigmine, physostigmine , di isopropyl florophosphate. b- Drugs that block NMT: e.g curare which competes with acetylcholine for its receptors on MEP. Changes Following Skeletal Muscle Stimulation A- Electric changes B- Excitability changes C- Mechanical changes  A- Electric changes The electrical events in skeletal muscle and the ionic fluxes underlying them are like those in nerve with some differences: The resting membrane potential of skeletal muscle is about - 90mV. The action potential lasts 2- 4 ms Is conducted along the muscle fiber at about 5 m/sec. The action potential precedes the contraction by about 2 msec  B- Excitability changes During the action potential, skeletal muscle fiber is refractory to restimulation. As the action potential precedes the muscle contraction, thus once the muscle begins to contract, it has regained its excitability and can respond to re-stimulation. Can be tetanized.  C- Mechanical changes Excitation contraction coupling: It is the mechanism by which action potential in the muscle initiates muscle contraction. It occurs through four steps: 1- Release of Ca2+. 2- Activation of proteins. 3- Generation of tension. 4- Relaxation. 1- Release of Ca2+:  Action potential spreads on both sides of the muscle and then propagated into the network of T- tubules. Its membrane contains a voltage-sensitive dihydropyridine (DHP) receptor. Activation of the voltage-sensitive dihydropyridine (DHP) receptor on T- tubules, opens the ryanodine Ca2+ release channel on the SR in the terminal cisternae leading to rapid Ca++ release.  Ca2+ binds to troponin.  Troponin undergoes conformational changes that causes tropmyosin to move away from its position covering the binding sites of myosin on actin. This leads to uncovering of the binding sites on actin.  Thus the heads of the bridges of myosin combines with the binding (active) sites on actin and contraction begins.  3- Generation of tension:  The tension developed during muscle contraction is generated by cross bridge cycling that occurs through four steps:  Binding of actin and myosin.  Bending of cross bridges and sliding of actin filaments across the thick filaments. This needs energy obtained from hydrolysis of ATP.  Detachment of cross bridges from the thin filaments and this needs new ATP. Return of cross bridges to original upright position and the cycle is repeated.  Cycling continues as long as Ca2+ is attached to troponin C and ATP is available. Tension is developed by bending of cross bridges. This tension is transmitted to Z lines and then to sarcolemma to tendons and to bones.  Muscle contracture For detachment of the cross bridges to occur, ADP and Pi must be removed from the cross-bridge and a new molecule of ATP put in their place. This new ATP reduces the affinity of the cross bridges for the active site. If no ATP is available, the thick and thin filaments cannot be separated (Muscle contracture). 4- Relaxation:  Ca2+ is removed from cytoplasm by the Ca2+ pump on the sarcoplasmic reticulum (SR). When Ca2+ concentration decreases intracellularly, troponin returns to its original state and tropomyosin covers active sites on actin. Cross-bridge cycling stops  The All or None Law: A single skeletal muscle fiber obeys all or none law in which the skeletal muscle fiber contracts maximally or does not contract at all. A threshold stimulus produces maximal contraction provided that the experimental conditions remain the same.