Structural muscle Proteins
- Titin: spans half of each sarcomere from z disc to M line. stabilizes the position of the thick filament. give muscle its elasticity and extensibility.
- alpha-Actinin: found in the Z disc. binds to actin molecules of the think filament and to titin
- Myomesin: found in the M line. Binds to titin and thick filaments to connect them together at the M line.
- Dystrophin: Cytoskeletal protein that links the think filaments to the sarcolemma. attached to the extracellular proteins in the connective tissues surrounding the muscle fibers. Helps transmit tension from the sarcromeres to tendons.
Sliding Filament Model
- Myosin ‘heads’ bind to actin to form a ‘crossbridge’
- Conformational change, energized by ATP hydrolysis, causes thin filaments to slide along thick filaments.
- Myosin head groups release, form new crossbridges, and the sliding cycle repeats.
Result: Z-lines move towards one another, Sarcomere length decreases, Myofibril shortens
Crossbridge cycling
- Cycle is entered following exposure of myosin binding sites on the actin thin filament (regulatory role for Ca2+).
- at the end of the last muscle contraction: 1. ATP binds to the myosin head. 2. This ATP is hydrolyzed by the unbound head, and the released energy results in a conformational ‘cocking’ of the head group
Contraction Cycle Steps
- Myosin binding sites on actin become exposed when Ca2+ binds to troponin.
- Myosin heads bind to actin forming crossbridges.
- Myosin heads pivot towards the center of tthe sarcomere (power stroke).
- ATP binds to the myosin head=> detachment of myosin head from actin.
- ATP is hyrolyzed and the energy released is used to re-energize the myosin head back to its start position so a new crossbridge can form
- The contraction cycle repeats until the myosin binding site on actin are no longer available.
Rigor Mortis
The rigor of death b/c lack of ATP to detach the crossbridge.
Events at Neuromuscular junction
- Electrical signal transmitted from a motor neuron to a skeletal muscle fiber (excitation).
- Triggers release of Ca2+from SR (EC coupling)
- Ca2+ binds to troponin on the thin filament, thereby permitting crossbridges to form. crossbridge cycling rresults in tension development (contraction)
- Removal of Ca2+ results in relaxation
Release of Ca2+ from the SR (excitation-contraction coupling)
- AP runs along sarcolemma, continues into T-tubules
- Triggers release of Ca2+ from SR
- Ca2+ diffuses into sarcoplasm and myofibrils
- Ca2+ binds to troponin on thin filament (myosin binding site on actin gets exposed.
- Crossbridges form=> tension is generated (starts contraction)
Relaxation- Sequestration of Ca2+
- When APs stop arriving at the NMJ, the trigger to release Ca2+ from the SR stops.
- Active Ca2+transporters in the SR membrane pump Ca2+ back into the SR
- Cytoplasmic [Ca2+] decreases
- As [Ca2+]cyto falls, Ca2+ comes off troponin- the myosin binding sites on actin get covered by tropomyosin
- Crossbridge cycling stops and tension drops
- titin brings the sarcomere back to resting position.
NMJ Excitation
- AP arrives at synaptic end bulb of motor neuron and causes opening of voltage gated Ca2+ channels
- Synaptic vesicles containing the neurotransmitter, ACh undergo exocytosis.
- ACh is released into the synaptic cleft and binds to ACh receptors on the sarcolemma (motor end plate).
- ACh receptors open and allow Na+ to enter the muscle fiber, generating an AP on the sarcolemma.
- ACh is quickly broken down to acetate and choline by acetylcholine Esterase (AChE)
Muscle Twitch
Contraction from a single electrical stiumulus e.g. and action potential
3 Periods
1. Latent: AP sweeps across sarcolemma, SR calcium ions released
2. Contraction: calcium binds to troponin, peak tension develops
3. Relaxation: Ca ions back into SR, Myosin binding sites on actin are covered by tropomyosin, tension decreases
Tetanus (or tetanic contraction)
summation over time (temporal summation) of individual twitches
-Tetanus is a mechanism for increasing tension
Motor Unit
A motor neuron and all the muscle fibers (cells) it innervates
-By activating (recruiting) increasing numbers of motor units, tension can be increased
Size Principle for Motor Units
The first motor units recruited are small (innervate few fibers)
- The result is fine, carefully controlled increase in tension.
- As more force is required, larger motor units are recruited.
Fiber Types
- Small, SO. SO=slow, oxidative. low force, low speed, high resistance to fatigue.
- Intermediate FOG. FOG= intermediate, oxidative-glycolytic (fatigue resistant). intermediate force, moderate speed, some resistance to fatigue
- Large, FG. FG= fast, glycolytic (fatiguable). large diameter (large force). high speed, low resistance to fatigue
Hypertrophy and Atrophy
- repeated, exhaustive stimulation increases muscle mass: hypertrophy. addition of more myofibrils (not more cells, not hyperplasia) and increase in mitochondrial and glycolytic enzymes
- A decrease in stimulation leads to a loss of muscle mass: atrophy.
Metabolic sources of ATP to support muscle contraction
ATP is immediate source of energy to develop tension (hydrolysis by the myosin head group fuels tension generation, then hydrolysis by the Ca-pump of the SR supports relaxation)
- Cell ‘pool’ of ATP: enough for 2 sec of maximal force
- Creatine Phosphate (CP) pool: CP stores ‘high energy phosphate’. CP pool support ~15 sec of maximal contraction (CP is 3-6 times more plentiful than ATP when muscle relaxed)
- Glycogen (used anaerobically- glycolysis): occurs in cytoplasm and can support 2 min of contraction
- Glycogen, fat and protein (used aerobically): occurs in the mitochondria relatively slow. can support 40 min to several hours of contraction
Cardiac Muscle (compared to skeletal)
- Function: pumps blood
- Structural Features: smaller cells (branched), less extensive T-tubule and SR system, myofibrils organized into sarcomeres, extensive cell-to-cell interactions (intercalated discs containing gap junctions and desmosomes)
- Function Issues: sliding filament model still applies. SR Ca2+ is not sufficient to support contraction; there is an obligatory need for extracellular Ca2+, No Motor Unit- every cell contracts with every beat as the electrical signal moves from cell-to-cell through gap junctions. everey contractions is a twitch
Smooth Muscle (compared to skeletal)
- Function: control diameter of tissue tubes
2. common structural features: small (single nucleus), lacks a clearly organized structure
Cori Cycle
- The muscle turns glucose to Lactic Acid
2. The liver turns Lactic Acid to glucose
O2 Debt
Cost of ‘resetting’ the system after exercise
- lactic acid conversion back to glycogen in the liver
- resynthesize creatine phosphate
- replace oxygen removed from myoglobin
- repair
Muscle Fibers
- Muscle cells are called fibers
- typically multinucleate (fusion of myoblasts)
- plasma membrane (sarcolemma) surrounds the cytoplasm (sarcoplasm)
- Myofibrils: longitudinal bundles of protein filaments inside the muscle fiber (acttin and myosin). Highly organized into ‘repeating units’ (sarcomeres)
