2 - Muscle physiology Flashcards
- Molecular aspects of muscle contraction: structure of skeletal muscle
- Myoblast: m.cells, formed by fusion of embryonic muscle cells
- Inner part densely packed w. myofibrils
- Myofibrils consists of myofilaments: actin and myosin
- Smallest unit of myofilaments is sarcomere.
- Consists of two sets of actin filaments, with myosin in betw.
- Sarcomere:
- Z-discs: divides the walls
- M-line: transverse line in the middle
- I-bands: zone containing only actin-light bands
- A-bands: zone containing both actin and myosin-dark bands
- Proteins: titin, nebulin, alpha-actinin
- Elements:
- Contractile components
- Serial elastic components (SEC)
- Parallel elastic components (PEC)
- Molecular aspects of muscle contraction: Types of muscle contraction
- Isometric: Only tension is changed but not the length of the m. Occurs during too heavy load.
- Isotonic: M. shortens with constant tension. Regular physiological behaviour.
- Auxotonic: In natural conditions, m. shortens and tension is also incr. in it. E.g. work against a spring.
- Preload: After stimulation contractile machinery will first stretch SEC elements (isometric period), and when tension reaches eq. with the load, contraction becomes isotonic, twitch is continued with shortening of the m.
- Afterload: If we block the free movement of the m. with a frame, then no more shortening is possible from a certain level, but m. is still able to incr. tension. At the beginning isotonic, then isometric.
- Muscle contraction
-The activation of tension-generating sites within muscle fibers
-Sliding filament mechanism:
•Shifting of myosin head by 45 degrees.
•Occurs after development of connections bw. myosin head and actin microfilament.
•Very short time course
1.Ca-ions binds to TnC2 -> tropomyosin molecules will move
2.Actin and myosin microfilaments bind to each other, ATPase is activated -> sliding occurs and connection bw. actin and myosin is released.
3.Myosin head binds ATP and will be repositioned to its original conformation.
4.If Ca2+ is present, a new cycle will start. If IC ca-signal is terminated–cross-bridge cycle stops.
•Result: approaching of Z-bands to each other, and shortening of the sarcomer length and the muscle itself.
- Electro-mechanical coupling
- The coupling which transforms an electrical impulse into a mechanical action
1. Neural AP is transferred to the muscle fibre at the myonerual junction area -> propagating AP on the myolemma.
2. The el.signal of myolemma reaches the triad through the system of T-tubuli, where it is tranformed into ca-signal: AP reaches the L-type Ca2+-channels in the T-tubuli -> L-type channels open
3. Because of this, ryanoid-Ca2+-chs will also open
4. From SR many Ca2+ will get into the IC part of the cell.
5. Ca2+-chs on the myolemma will also open (Ca2+-influx from the EC)
6. Result: IC Ca2+ level incr. around the sarcomer -> contraction
7. Relaxation: ca-elimination to the SR and/or to other compartments
- Types of striated muscles
- Muscle tissue fibres:
1) Fast twitch fibre: capable of powerful contraction. Cover E needs by anaerobic glycolysis: phasic muscles.
2) Slow twitch fibres: capable of sustained work. Gain E only from glu oxidation: tonic muscles.
3) Intermediate types: usually intermixed in most of the muscles: % of these fibre types determine the type to which a muscle belongs. - Pink phasic muscle/White phasic muscle/Red tonic muscle:
1. ATPase type: fast / fast / slow
2. SR pump: fast / fast / slow
3. Junction/fibre: 1/1 / 1/1 / “en grappe”-type
4. T-system: developed / very developed / not developed
5. Muscle AP/neural AP: excists/very frequent / excists/very frequent / no/rare
6. Contraction time: 20 / 10 / 200
7. Metabolism: mixed / anaerobic / oxidative
8. Fatigue: slow / fast / no
9. Fibre length: intermediate / very long / very short
- Energy source of muscle functioning
- ATP: Both contraction+ relaxation need ATP. ATP conc. of myocyte:5 mmol/l, covers O2 need for 2-3 sec only
- Creatin-phosphate: Provides E reserve for short term, intensive contraction. Conc. of myocyte CRP: 20 mmol/l, E-supply for 20-30 sec.
- Anaerobic glycolysis: in case of outstanding load. E-source can be: glycogen(for fast movement; glycogenolysis), glucose(prolonged, long term contraction).
- Oxidative phosphorilation: very-long term muscle activity (Red-muscles). Pyruvate transformed to AcCoA.
- Oxygen debt
- Muscles using anaerobic glycolysis will resynthesize prev. depleted energy stores after work. Resynthesis is under aerobic conditions.
- Muscles can replenish glycogen, creatine-phosphate, etc., by O2-consumption.
- Macroscopic events of muscle contraction
-Macroscopic investigation of muscle function:
1. Elements of contraction: CC (contraction component) = sarcomer
2. Elastic elements: SEC (serial elastic comp.), PEC (parallel)
•Types of contraction:
o Twitch:
o Isotonic contraction: contraction with constant tension, regular physiol. activity.
o Isomertric contraction: tension is changed (not length), lifting too heavy load
o Mixed contraction forms: comb. of isometric and isotonic
- Auxotonic: working against incr. tension, resistance (i.e. against a spring)
- Preload: After stimulation. Muscle length adjusted with (pre)load (isometric), then isotonic contraction. (e.g. locomotion)
- Afterload: contraction begins with isotonic, then blocking of contraction with a load (isometric) (e.g. biting, chewing)
• All-or-none: How a single fiber under constant metabolic conditions contracts: to an adequate stimulus- response is maximal, to smaller stimulus - no response.
•Quantal summation: If the incr of tension is caused by participation of more and more fibers. If demand is higher, a more frequent AP recruits more and more fibers.
•Contraction summation: Repetitive stimuli may cause incr contraction, for the previous Ca transient may not be completed when a new stimulus elicits additional Ca release. Thus, amplitude of contraction is incr.
•Staircase effect: New stimuli applied shortly after the end of a twitch may elicit new contractions with gradually increasing amplitudes: it is caused by IC Ca, which has no time to be removed bw stimuli (warming up).
•Tetanus: If we apply stimuli with incr frequency we enhance possible summation modes: finally muscle reaches maximal contraction state
- length-tension diagram: working range and power of the muscle
-Length-tension curve: obtained when one stimulates muscles with max single impulses. The muscles are passively stretched with varying loads.
-As a result of isotonic, isometric, preload or afterload experiments we can construct the range where the muscles execute normal physical work.
-Work = Length x Tension (load)
1) Isotonic maximum curve: If we passively stretch the muscle to A, B, C distances above the resting length (L0) and in these positions stimulate the muscle with max stimuli
2) Isometric maximum curve: If no shortening is possible
3) Preload-maximum curve: preload conditions
4) Afterload-maximum curve: afterload experiments
•As a sum of the experiments we can construct the area of the physiological working range of a muscle.
•Skeletal muscle: length measured under maximaln power is identical to the normal working range of the muscle.
•Cardiac muscle: normal working range is much below the length, which would ensure maximal tension: i.e., cardiac muscle has a reserve
-Work: consists of outer work and inner work.
-Total work of a muscle: measured from its oxygen consumption: Wt = Wo + Wi
*Efficiency: Wo/Wt = approx. 20%
- length-tension diagram: heat production
•Partly caused by ATP breakdown during contraction and by synthetic processes after contraction.
-3 main phases:
1. Resting: A considerable ratio of basal metabolic rate comes from heat prod. of muscles.
2. Initial: At the beginning of contraction.
o Activation: electromechanical coupling
o Contraction: sliding filaments and calcium pumps
3. Restitution: Fast muscles generate contractile energy by utilization of their energy stores. After contraction, these stores must be filled up again: synthesis results in energy investment and heat prod.
-Fast, glycolytic, white fibers:
o Initial heat is much larger than restitution heat.
o High power for a short period is possible.
o Muscle “pays back” its oxygen debt during re-synthesis of energy reserves.
- Slow, oxidative, red fibers:
o After short initial glycolytic phase of heat production, a long lasting oxidative period begins.
o Muscle is not exhausted and there is no oxygen debt.
- length-tension diagram: muscle fatigue
- Muscle fatigue: decr. ability of a muscle to generate force.
- Can be a result of vigorous exercise, but abnormal fatigue may be caused by barriers to or interference with diff stages of muscle contraction.
- There are two main causes of muscle fatigue:
1. Limitations of a nerve’s ability to generate a sustained signal (neural fatigue)
2. Reduced ability of the muscle fiber to contract (metabolic fatigue) - Depends on ratio of glycolytic and oxidative fibers of the muscle
- Two main factors:
1. Shortage of fuel (substrates) within muscle fiber
2. Accumulation of metabolites within muscle fiber, which interfere either with release of calcium or ability of calcium to stim muscle contraction.
-Signs of fatigue:
o Decrease of twitch amplitude
o Increase of twitch duration
-In vitro fatigue: After fatigue, restitution takes place faster if the environment is abundant in oxygen. In nitrogen-rich environment, muscle reaches an unrecoverable fatigue state.
-In vivo fatigue:
o Peripheral fatigue, a consequence of: Decr E stores, incr by-product concentration, direct effect of lactic acid
o Central fatigue, after long term tension: exhaustion of motor unit/of myoneural junction.
-Fatigue is developing earlier in fast, glycolytic, phasic fibers than in tonic, oxidative fibers.
-Subjective feelings of fatigue: Increased heat production, Decrease of pH, Direct effect of lactic acid, Dehydration, general hypoglycaemia
- The regulation of muscle work and muscle nerve connection
•Muscle-nerve connection: The transmission of neural AP to the muscle
*Takes place in the area of the myoneural junction.
*Acetyl choline release induced by AP at nerve terminals, binds to nicotinic receptors of muscle membrane and results in opening of ligand activated cationic channels.
*This prod. a local current which is gradually decreasing conducted to the voltage gated Na channel. There, a sudden conformation change is induced and AP is formed
•Presynaptic area: AP from axon. Neural AP induces ca entry to the synaptic ending. Acetylcholine vesicle release.
•Synaptic cleft: Filled with acetylcholine
•Postsynaptic area: Acetylcholine binds to its specific receptors on myolemma. Ligand gated ion channel is opening: a local end plate potential (EPP) is developing. EPP activates neighboring voltage gated Na channels, which result in a formation and propagation of APs.
- The regulation of muscle work and muscle nerve connection: the motor unit
•Composed of: a nerve and a muscle supplied by this nerve.
•Large motor unit: glycolytic, anaerobic, white, phasic fibres
o Nerve: Large diameter, very fast conduction, difficult stimulation
o Muscle: Large fiber number, large diameter, large force, anaerobic metabolism, speed is fast, easily fatigues, fiber length is very long.
•Small motor unit: tonic, aerobic, red fibres
o Nerve: Small diameter, fast conduction, easy stimulation
o Muscle: Few fiber number, intermediate diameter, small force, oxidative metabolism, speed is slow, does not fatigue, fibre length is short.
- Characteristics of smooth muscle
-Non-striated muscle
•Comprises about 3% of the body mass
•2 major types:
1. Single-unit SM: in walls of hollow and tubular organs
*Whole bundle/sheet contracts as a syncytium
*Electrically connected by gap junctions that facilitate synchronized contractions.
*Sustained contraction transfers pressure to the content/organ, while alternating contractions and relaxations -> mixing of content
*Can create waves of contraction = peristaltic movements
2. Multi-unit SM: primarily in eyes and skin
*Lacks gap junctions: can contract independently
*Responsible for: adjusting diameter of pupils according to intensity of light, altering curvature of the lens in the eye and hanging angle of hairs relative to skin surface
-Diameter; less than 0,01 mm, length; 0,1-0,2 mm.
-Develop from one cell and have only one nucleus.
-Can be formed throughout life.
-Contain actin and myosin filaments, but not organized in sarcomers. Longer than in skeletal muscle, and arranged in bundles of diff orientation.
o In cytoplasm, actin filaments are attached to dense protein lattices, analogous to the Z-discs
o Myosin filaments are located bw actin filaments. The ends on myofilaments bundles are attached to protein plates in the cell membrane.
o Bundles of intermediate filaments bw membrane plates, and bw the dense bodies in cytoplasm.
-Adjacent cells connected by proteins fibers bw the protein plates in the membrane
-Cells are also anchored to collagen fibers in EC matrix
-Lack T-tubules
-SR is poorly developed compared to skeletal muscle
- Characteristics of smooth muscle: contraction
1) Stimulation of the cells result in incr. ca conc. in the cytosol, due to ca-ion-chs and ca release from SR.
2) Ca binds to calmodulin
3) Ca-calmodulin complex activates myosin kinase.
4) Myosin kinase transfers a P-group from ATP to the myosin heads.
5) Myosin heads hydrolyze ATP and bind to actin.
6) Cross-bridges are formed and broken causing the cell to contract.
7) When stimulation of the cell ceases, ca pumps in the cell memb. and SR will remove ca from the cytosol.
8) The ca conc. in cytosol falls, ca dissociates from calmodulin, and the activation of myosin kinase ceases.
9) Myosin phosphatase dephosphorylates the myosin heads, which then lose their ATPase activity and the ability to bind to actin.
10) The muscle cell relaxes.
