Muscle Physiology LC4 PDF

OUTLINE I. NERVE ACTION POTENTIAL a. Neuromuscular and Synaptic Transmission b. Action Potential c. Events that Occur in an Action Potential i. Resting...

OUTLINE I. NERVE ACTION POTENTIAL a. Neuromuscular and Synaptic Transmission b. Action Potential c. Events that Occur in an Action Potential i. Resting Membrane Potential ii. Depolarization iii. Repolarization II. REFRACTORY PERIOD a. Absolute Refractory Period b. Relative Refractory Period III. CONTRACTION AND EXCITATION OF SKELETAL MUSCLE a. Steps in the Excitation-Contraction Coupling in Skeletal Figure 2. Diagram of an action potential. Muscle IV. LENGTH-TENSION AND FORCE VELOCITY RELATIONSHIPS IN - The overshoot is the brief portion at the peak of the action potential MUSCLE when the membrane potential is positive. a. Isometric Contraction b. Isotonic Contraction EVENTS THAT OCCUR IN AN ACTION POTENTIAL c. Length-tension relationship d. Force velocity relationship V. CONTRACTION AND EXCITATION OF SMOOTH MUSCLE 1. Resting Membrane Potential a. Types of Smooth Muscle - Resting membrane potential is at 70mV, cell negative b. Steps in the Excitation-Contraction Coupling in Smooth - It is sometimes known as the polarized state Muscle - A result of high conductance of K+ - Inactivation gates of Na+ are open but the channels are close - The K+ channels are also closed during this state I. NERVE ACTION POTENTIAL Neuromuscular and synaptic transmission - An action potential in the presynaptic cell causes depolarization - Calcium enters the presynaptic terminal releasing neurotransmitters - Neurotransmitter attached to the postsynaptic cell membrane - Inhibitory neurotransmitters hyperpolarize the postsynaptic membrane Figure 3. Structure of the Na+ channel and K+ channel during resting membrane potential. Table 1. Locations of ions with respect to the cell Outside the cell (Extracellular) Inside the cell (Intracellular) Na+ (primary extracellular K+ (primary intracellular cation) cation) Cl- Other negative anions Ca2 Remember: PiSo (Potassium In, Sodium Out) Figure 1. Transmission of a nerve action potential to a muscle cell. 2. Depolarization Action Potential - Rapid opening of Na+ channels (The activation gate of the Na+ - Is a property of excitable cells (i.e., nerve, muscle) that consists of a channel in the nerve is opened) rapid depolarization, or upstroke, followed by repolarization of the - Equilibrium is now driven by Na+ due to its influx membrane potential. Page 1 of 6 [PHYSIOLOGY] 1.04 MUSCLE PHYSIOLOGY – Dr. Navid P. Roodaki, MD SUMMARY Figure 4. Opening of Na+ channels, causing their influx to the cell. - Inactivation gates of Na+ channels is closed The same increase in voltage that opens the activation gate also causes the inactivation gate to close. However, this closing of the inactivation gate is a few 10,000th of a second delayed after the activation gate opens When this happens, sodium ions can no longer enter the membrane, and the membrane potential begins to return towards the resting membrane potential → repolarization. - This inactivation process of the sodium channel will cause the inactivation gate not to reopen until the membrane potential goes back or is close to the level of resting membrane potential. - It is not usually possible to open the sodium channels again without repolarizing the nerve fiber first. Note: P stands for permeability (e.g. PNa+ = permeability of Na+) II. REFRACTORY PERIOD Figure 5. Closing of the inactivation gate of Na+ channel Absolute Refractory Period - Another action potential cannot be elicited, no matter how large the - It also opens the K+ channels and increases potassium conductance stimulus - Coincides with almost the entire duration of the action potential - The opening of K+ channels are slightly delayed, hence - Due to closure of the inactivation gates they open by the same time the Na+ start to close due to inactivation. Relative refractory period - The membrane potential becomes less negative (the cell - Begins at the end of the ARP until resting level interior becomes less negative). - Action potential can be elicited if larger than usual inward current is provided 3. Repolarization - It opens the K channels to a greater degree than normal - Due to the closing of Na+ channels and opening of K+ channels making K+ conductance higher - Primarily due to the outflux of K+ ions - The membrane potential becomes more negative (the cell interior becomes more negative) Figure 7. Refractory Periods Propagation of Action Potential Figure 6. Opening of K+ channels. - Direct Propagation: excitable membrane has no single direction of propagation (multi-directional) - All-or-nothing principle: once an action potential has been elicited at any point on the membrane of a normal fiber, the depolarization process only occurs when the condition is right. Page 2 of 7 [PHYSIOLOGY] 1.04 MUSCLE PHYSIOLOGY – Dr. Navid P. Roodaki, MD Conduction velocity is increased by: A. Increase fiber size - Increasing the diameter of a nerve fiber results in decreased internal resistance; thus, conduction velocity down the nerve is faster. B. Myelination - Myelin acts as an insulator around nerve axons and increases conduction velocity. III. CONTRACTION AND EXCITATION OF SKELETAL MUSCLE - Each muscle fiber is multinucleated and behaves as a single unit - It contains bundles of myofibrils surrounded by SR invaginated by transverse tubules (T tubules) - Each myofibrils interdigitating thick and thin filaments arranged longitudinally in sarcomeres - Sarcomere: the smallest part of a muscle fiber that is capable of contraction. - Repeating units of sarcomere accounts for the unique banding pattern in striated muscle - A sarcomere runs from Z line to Z line Figure 9. A: Myosin molecule. B: Myosin filament together with the cross-bridges in the myosin head and the interaction of the heads of the cross-bridges with adjacent actin filaments Thin filaments - Anchored at the Z line Z line: where the ends of actin filaments are attached; the area between two Z lines is called the sarcomere - Present in I bands (“I” = “thin”) I bands: light bands that only contains actin filaments - Contain actin, tropomyosin and troponin - Troponin is a complex of three globular proteins: - Troponin T (tropomyosin) attached the troponin complex to tropomyosin - Troponin I (inhibition) inhibits the interaction of actin and myosin - Troponin C (calcium) in the Ca binding protein that permits interaction of actin and myosin Figure 8. Structure of the sarcomere in the skeletal muscle. A: Arrangement of thick and thin filaments. B: Transverse tubules and sarcoplasmic reticulum. Thick filaments - Present in the A bands in the center of the sarcomere A bands: dark bands in the sarcomere that contains myosin filaments as well as the overlap of myosin and actin filaments - Contain myosin - Composed of >200 individual myosin molecules that when bundled together, they form the body of the filament while several heads of these molecules hang outward to the sides of the body - A part of each myosin molecule’s body hangs to the side together with the head, hence giving an arm that extends the head away from the body – together, the protruding arms and head are called cross-bridges Figure 10. Thin filament composition. - Each of these cross-bridges are flexible at two points which are called hinges – one where the arm leaves the M line myosin filament’s body and one where the head attaches - Vertically extends down the middle of the A band within the center to the arm. These hinged arms allow the heads to be of the H zone either extended outward away from the body or be pulled close to the body H zone - The lighter part in the middle of the A band where the thin filaments do not extend to T tubules - Extensive tubular network, open to extracellular space that carry the depolarization from the sarcolemma membrane to the cell interior - Are located at the junctions of A bands and I bands - Contains voltage-sensitive protein called the dihydropyridine receptor Page 3 of 7 [PHYSIOLOGY] 1.04 MUSCLE PHYSIOLOGY – Dr. Navid P. Roodaki, MD - Area where entries of Ca2+ and the different ions occur in order for the action potential or the contraction to actually occur C Figure 13. The thin filament with Ca2+ ions. A: Cross-sectional view of the components of the thin filament with the myosin head. B: Attachment of Ca2+ to troponin, causing tropomyosin to have a conformational change and expose the myosin cross-bridge binding site. C: Cross-sectional view of the cross-bridge caused by Ca2+ ions. Figure 11. Structure of the T-tubule. The “Walk-Along” Theory of Contraction - When the myosin head and the myosin-binding site of the actin Sarcoplasmic reticulum (SR) filament make contact at the cross-bridge, the shape of the bridge - Internal tubular structure that is the site of Ca2+ storage and release changes as it bends inward at a 45° angle and pulls the actin filament for excitation-contraction coupling with it. This action is called the power stroke - Contains a Ca2+ release channel called the ryanodine receptor - These power strokes are directed to the center of the sarcomere - On each side of the sarcomere, the thin filaments are STEPS IN THE EXCITATION-CONTRACTION COUPLING IN SKELETAL MUSCLE pulled toward the center of the A band, pulling together Step 1: Action potential in muscle membrane the Z line where they are attached to. This leads to the initiate depolarization of the sarcolemma that spreads to the T shortening of the sarcomere tubules - Sliding-filament mechanism: the shortening of the entire Step 2: Depolarization of the T tubules muscle fiber due to the simultaneous shortening of the causes a conformational change in its dihydropyridine receptor, sarcomeres which opens Ca2+ release channels (ryanodine receptors) in the nearby SR, causing release of Ca2+ from the SR into the intracellular fluid Step 3: Increase of intracellular calcium FIgure 14. The “walk-along” mechanism for muscle contraction. Figure 12. Effect of the action potential on the T tubule of a muscle cell. Step 4: Calcium binds to troponin C causing a conformational change in troponin that moves tropomyosin out of the way Figure 15. All thin filaments that surround each thick filament are simultaneously pulled inward through the cross-bridge cycles during muscle contraction. ATP as the Energy Source of Muscle Contraction - Large amounts of ATP are cleaved into ADP and inorganic phosphate by the activity of the ATPase in the myosin head during the process A of contraction - The greater the amount of work executed by the muscle, the greater the amount of ATP cleaved. This is called the Fenn effect B Page 4 of 7 [PHYSIOLOGY] 1.04 MUSCLE PHYSIOLOGY – Dr. Navid P. Roodaki, MD IV. LENGTH-TENSION AND FORCE VELOCITY RELATIONSHIPS IN MUSCLE Isometric Contraction - Measured when length is held constant No shortening of muscle - Muscle length is fixed, the muscle is stimulated to contract - The developed tension is measured - The load is greater than the force of the contraction of muscle - The muscle makes tension when it contracts, but the length of the muscle is still the same Figure 16. The cross-bridge cycle which shows ATP as the energy source. Rigor Mortis - Several hours after death, all the muscles of the body go into a state of contracture Figure 19. Muscle in an isometric contraction - Muscles contract and become rigid even without action potentials - Rigidity results from loss of all the ATP which is required to cause Isotonic Contraction separation of the cross-bridges from the actin filaments during the - Measured when load remain constant relaxation process. - There is shortening - The force of the contraction of the muscle is greater than the load Step 5: Relaxation - The tension on the muscle remains the same during contraction - After an action potential or during repolarization, Ca2+ will be taken - When the muscle contracts, it decreases in length and moves the up by the sarcoplasmic reticulum by ATP-dependent calcium pumps load Figure 17. Effect of repolarization on the T tubule of a muscle cell. - With the absence of Ca2+ ions in the sarcoplasm, there will be no Ca2+ ions attaching to troponin, hence tropomyosin returns to its original position, covering the myosin cross-bridge binding sites on actin - Contraction also stops, and the thin filament slides back to its original position Figure 20. Muscle during isotonic contraction Length-tension relationship - Measures tension developed during isometric contraction ○ Passive tension: tension developed by stretching muscle ○ Total Tension: when muscle is stimulated to contract ○ Active tension: difference between the two Represents the active force developed from contraction of the muscle It is proportional to the number of cross-bridges formed Figure 18. Relaxed muscle fiber. Page 5 of 7 [PHYSIOLOGY] 1.04 MUSCLE PHYSIOLOGY – Dr. Navid P. Roodaki, MD Figure 23. Visceral and Multiunit smooth muscles. Figure 21. Relationship of the length of the muscle to the tension in the muscle before and during the contraction of muscle. STEPS IN THE EXCITATION-CONTRACTION COUPLING IN SMOOTH MUSCLE - The mechanism of excitation–contraction coupling is different from Force velocity relationship that in skeletal muscle. - Measures the velocity of shortening of isotonic contraction - There is no troponin; instead, Ca2+ regulates myosin on the thick filaments. FIgure 22. Relation of load to the velocity of a skeletal muscle contraction with a cross section of 1 cm2 and a length of 8 cm. V. CONTRACTION AND EXCITATION OF SMOOTH MUSCLE Smooth Muscle - has thin and thick filaments that are not arranged in sarcomeres Types of smooth muscle: 1. Multiunit Smooth muscle - Present in the iris, ciliary muscle of the lens, and vas deferens - Behaves as a separate motor unit - Little or no electrical coupling between cells Figure 24. Mechanism of muscle contraction in smooth muscle - Densely innervated Step 1: Depolarization of the cell membrane 2. Unitary Smooth muscle - opens voltage-gated Ca2+ channels and Ca2+ flows into the cell down - Most common type its electrochemical gradient, increasing the intracellular [Ca2+]. - Seen in the Uterus, GIT, Ureter, Bladder Step 2: Intracellular [Ca2+] increases. - High degree of electrical coupling between cells Step 3: Ca2+ binds to calmodulin. - The Ca2+ – calmodulin complex binds to and activates myosin light 3. Vascular Smooth muscle chain kinase. When activated, myosin light chain kinase (MLCK) - Both multiunit and single unit phosphorylates myosin and allows it to bind to actin, thus initiating cross-bridge cycling. The amount of tension produced is proportional to the intracellular Ca2+ concentration. 4. A decrease in intracellular [Ca2+] produces relaxation. Page 6 of 7 [PHYSIOLOGY] 1.04 MUSCLE PHYSIOLOGY – Dr. Navid P. Roodaki, MD Figure 25. Mechanism of muscle relaxation in smooth muscle References: Costanzo, L. S. (2015). BRS Physiology 6th Edition. 351 West Camden Street Baltimore, MD 21201 Hall, J. E. (2016). Guyton and Hall Textbook of Medical Physiology (13th ed.). Philadelphia: Elsevier, Inc. Sherwood, L., Klandorf, H., & Yancey, P. H. (2013). Animal Physiology: From Genes to Organisms (2nd ed.). Belmont: Brooks/Cole, Cengage Learning Page 7 of 7