Changes Following Skeletal Muscle Stimulation PDF

Changes followin skeletal muscle stimulation Dr. Hader I. Sakr Associate professor, Medical Physiology Learning objectives: Electrical changes. Excitability changes. Mechanical changes. Types of muscle contractions. Metabolic changes. Electrical and Excitability changes  Electrical a...

Changes followin skeletal muscle stimulation Dr. Hader I. Sakr Associate professor, Medical Physiology Learning objectives: Electrical changes. Excitability changes. Mechanical changes. Types of muscle contractions. Metabolic changes. Electrical and Excitability changes  Electrical and Excitability changes (A) Electrical Changes : - The electrical events in skeletal muscle and the ionic fluxes underlying them are similar to those in nerve, with few quantitative differences in timing and magnitude. - The RMP of skeletal muscle is about - 90m V. - The AP spike lasts 2-4 ms and is conducted along the muscle fiber at about 5 m/sec. - The AP precedes the contraction by about 2 msec.  Electrical and Excitability changes (B) Excitability Changes : - Skeletal muscle fiber, like nerve fiber, is refractory to re- stimulation during the AP. - The latent period of the mechanical response coincides the ARP of the AP. - It will be noted that as the muscle begins to contract, it has regained its excitability. Mechanical changes  Mechanical changes - It is the process by which an AP initiates the contractile process. It involves 4 steps:  Mechanical changes 1. Release of Ca2+: The propagation of the AP into the T tubules DHP pulling the feet processes open Ca2+ channels on the terminal cistemae Ca2+ flows out of the TC into the sarcoplasm. 2. Activation of muscle proteins: When sarcoplasmic [Ca2+] ≥ 0.1 μmol/L, Ca2+ binding to troponin C on the thin filament troponin conformational change tropomyosin moves away from its position covering the myosin-binding site on actin the binding site on actin combines with the cross-bridges binding sites from the thick filament contraction begins.         Mechanical changes  Mechanical changes 3. Generation of tension: Tension (the force developed when a muscle contracts) is generated by the cycling of the cross-bridges which occurs after they bind to the thin filament. In a rested, non-contracting muscle, myosin exists in a high-energy conformational state (M*). Both the ATP molecule and its hydrolyzing enzyme (myosin ATPase) are attached to the cross- bridge. The energy of ATP hydrolysis is used to drive myosin from a low-energy conformational state (M) to the high-energy state (cooked), as depicted in the following equation: (M-ATP) (M*-ADP-Pi)  Mechanical changes A. The 1st step in the cross-bridge cycle is the binding of actin and high-energy myosin (M*-ADP-Pi) (cooked). B. The 2nd step is the bending of the cross-bridges (aided by Actomyosin ATPase) and the sliding of the thin filament across the thick filament with conversion of myosin to its low-energy conformational state (M-A). - These events are accompanied by simultaneous translocation of the attached thin filament toward the M line of the sarcomere).  Mechanical changes C. The 3rd step is the detachment of the cross-bridge from the thin filament. - For detachment to occur, a new molecule of ATP is needed. - 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- rigor). D. The final step, the cross-bridges return to their original upright position through ATP hydrolysis to drive myosin from a low-energy to the high-energy (cooked) state: (M-ATP) (M*-ADP-Pi)  Mechanical changes - Cycling continues as long as Ca2+ is attached to troponin & energy is available. - The force developed by the cross-bridge bending is transmitted through the actin filament to the Z disk & then through the sarcolemma and tendinous muscle insertions to the bones. 4. Relaxation: occurs when the Ca2+ is removed from the cytoplasm by Ca+2/ATPase pump located on the SR membrane. - When IC [Ca2+] falls to ˂ 0.1 μmol/L, troponin returns to its original conformational state, tropomyosin moves back to over myosin binding site on actin, and cross-bridge cycling stops.  Mechanical changes The All or None Law: - A single skeletal muscle fiber obeys the all or none law. 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. The Muscle Twitch: A single AP causes a brief contraction followed by relaxation. - This response is called simple muscle twitch. - The twitch starts about 2 msec after the start of depolarization of the membrane and before repolarization is complete.  Mechanical changes Phases: 1. Latent period: Time between stimulation and start of contraction. Causes: a) Conduction of impulse. b) Synaptic delay. c) Time needed to initiate electrical and mechanical events in the muscle. d) Viscosity of the muscle tissue. e) Inertia of the lever system (not with modern devices). 2. Contraction phase. 3. Relaxation phase. 4. Recovery period. Type of muscle contractions  Type of muscle contractions - There are 2 types of muscle contraction: 1-Isometric contraction. 2-Isotonic contraction. - The skeletal muscles contain, in addition to the contractile element (CE), elastic and viscous elements in series with the contractile element and present mainly in the tendons, the series elastic component (SEC). Type of muscle contractions Type of muscle contractions  Type of muscle contractions 1- In isometric contraction, there is no much sliding of myofibrils along each other’s, in contrast to isotonic contraction. 2- In isotonic contraction a load is moved a distance, which involves the phenomenon of inertia and momentum that interfere greatly with the record of the twitch. Therefore, isotonic contraction lasts longer and needs a greater amount of energy than isometric contraction. 3- Isotonic contraction does external work since the load is moved a distance. However, in isometric contraction since load X distance = zero, no external work is done by the muscle and the mechanical efficiency is zero. 4- The mechanical efficiency (the percentage of energy input that is converted into work instead of heat) is about 20-25%.  Type of muscle contractions 5- Isotonic contraction evokes movement of part of the body or the body as a whole. On the other hand, Isometric contraction tenses a part of the body and maintains the posture against gravity. Isotonic contraction Isometric contraction Tension changes No change Tension increases Length changes (external) Muscle shortens = Sliding No Changes = No Sliding Duration & Energy Last longer & consumes more Last shorter & consumes less energy ( To overcome inertia & energy ( No inertia or momentum) Momentum) External work Present (Load is moved) No External work Mechanical efficiency 20 – 25 % Zero Importance Moves part of the body Tenses a part of the body  Type of muscle contractions When standing, person tenses the quadriceps muscles to tighten the knee joints and to keep the leg stiff (isometric contraction). During running, contractions of leg muscles are a mixture of isometric (when the legs hit the ground) and isotonic contractions (to move the limbs). When a person lifts a heavy weight using the biceps, the contraction starts isometrically and completed isotonically. With heavier loads, the duration of isometric contraction phase is longer while the he rate and extent of muscle shortening during isotonic contraction is less. Metabolic changes  Metabolic changes Energy Sources and Muscle Metabolism: I- During Rest: The skeletal muscles consume energy for: a) Maintenance of the RMP (5%). b) Synthesis of chemical substances e.g. glycogen. c) Production of Muscle tone. II- During Contraction: Energy consumption is markedly increased. - ATP is the only immediate energy source for the contraction of muscle. - ATP is hydrolyzed anaerobically into ADP and the muscle protein myosin acts as the enzyme ATPase. Myosin ATP + H 2 ⎯⎯⎯ ATPase → ADP + H3PO 4 + E 1200 Cal. - ATP inside the muscle is not enough except for 5 or 6 seconds maximal contraction. - Therefore, ATP is reformed continuously by means of three different metabolic mechanisms:  Metabolic changes - (1) Phosphocreatine: Creatine ~ PO3 - Most muscle cells have 2 to 3 times as much phosphocretine as ATP. - Energy transfer from phosphocreatine to ATP within a small fraction of second. - The cell phosphocreatine + ATP called the phosphogen energy system. - These together can provide maximal muscle power for a period of 10 to 15 seconds, enough for 100 m run. - Creatine phosphate is later restored by means of the reverse reaction during muscle relaxation.  Metabolic changes (2) The Glycogen lactic Acid system : - Under optimal conditions the glycogen-lactic acid system can provide 30 to 40 second of excess muscle activity in additions to those provided by the phosphogen system. Anaerobic Glu cos e + 2ATP [or glycogen +1 ATP] ⎯⎯⎯⎯→ Glycolysis 2 lactic acid + 4 ATP. in cytoplasm - Lactic acid causes extreme fatigue which serves as a self-limitation to further use of this system for energy.  Metabolic changes - Under optimal conditions the glycogen-lactic acid system can provide 30 to 40 sec of excess muscle activity, in additions to the phosphogen system. - Removal of the lactic acid from all the body fluids requires an hour or more and is achieved in three ways: 1. Some of the lactic acid is converted to pyruvic acid then metabolized oxidatively by all body tissues (citric acid cycle, slow mechanism). 2. Much of the lactic acid is reconverted to glucose by the liver, which in turn is used mainly to replenish the glycogen stores of the muscles. 3. It is used as a fuel in the heart.  Metabolic changes (3) The Aerobic System : - Means oxidation of food stuffs (glucose, fatty acids and amino acids) in the mitochondria to provide energy. Oxygen Glu cos e+ 2 ATP [or glycogen + 1 ATP] ⎯⎯⎯ → 6 CO 2 + 6 H 2O + 40 ATP - It is sufficient for an unlimited time “as long as nutrients and O2 are available and can compensate for muscular energy expenditure.  Metabolic changes - During muscular exercise, the muscle blood vessels dilate and blood flow is increased so that the available O2 supply is increased. - Up to a point, the increase in O2 consumption (INPUT) is proportional to the energy expended (OUTPUT), and all the energy needs are met by aerobic processes. - When muscular exertion is very great, some ATP synthesis is accomplished by using the anaerobic pathway when ATP, creatine phosphate stores and oxygen supply from myoglobin are depleted. Metabolic changes  Metabolic changes II- During Contraction: System Time Phosphogen 10 - 15 seconds Glycogen - lactic acid 30 – 40 seconds Aerobic Unlimited time “as long as nutrients and O2 are available - Thus we can readily see that the phosphogen system is the one utilized by the muscle for power surges, aerobic system is required for prolonged athletic activity. Glycogen-lactic acid system important for giving extra power during such intermediate races as the 200 to 800-m runs. - FFA is probably the major substrates for muscle at rest and during recovery from contraction.  Metabolic changes Ill- During recovery (oxygen Debt):  Metabolic changes - After a period of exertion is over, the rate of ventilation remains high for some time, extra O2 is consumed to: 1. Remove the excess lactate. 2. Replenish the ATP, and creatine phosphate stores. 3. Replace the small amounts of O2 that have come from myoglobin. - This extra post-exercise O2 consumption is called [oxygen debt]. Conclusion Electrical and excitability changes following skeletal muscle action potential are the same as those in the nerves with few differences. Mechanical changes entrails the occurrence of active tension and active relaxation. Muscle contraction may be isokinetic, isometric or isotonic. Metabolic changes are present during rest, activity and recovery. References Guyton and Hall, 13th edition. Unit II(6); 82-4. Ganong’s review of medical physiology 25th ed. Section I(5); 103-5, 108-9. Thank You