Skeletal Muscle Contraction Physiology Skeletal Muscle Contraction

Connective Tissue Endomysium Perimysium Epimysium Surrounds each muscle fiber (cell) Attaches to Z-lines in each sarcomere Perimysium Surrounds bundles (fascicles) of muscle fibers Attaches to endomysium Epimysium Attaches to the Perimysium Continuous with tendon

Sarcomere Repeating Patterns within the myofibrils Myofibrils Proteins within the myofibers Myosin Actin

Muscle Anatomy Sarcolemma Myofibrils Muscle fiber cell membrane Highly organized bundles of contractile and elastic proteins Carries out the work of contraction

Contain 6 types of protein: Myofibrils = Contractile Organelles of Myofiber Contain 6 types of protein: Actin Myosin Tropomyosin Troponin Titin Nebulin Contractile Regulatory Accessory

Titin and Nebulin Titin: biggest protein known (25,000 aa); elastic! Stabilizes position of contractile filaments Return to relaxed location Nebulin: inelastic giant protein Alignment of A & M

Changes in a Sarcomere during Contraction

Myosin Myo- muscle Motor protein of the myofibril Thick filament Attaches to the M-line Heads point towards Z-lines Myosin heads are clustered at the ends of the filament Myosin tails are bundled together

Role of calcium Troponin and Tropomyosin bind to actin Troponin complex Troponin and Tropomyosin bind to actin block the actin – myosin binding sites Troponin is a calcium binding protein

Actin Thin Filament Globular protein Attached to Z-lines G-Actin Has binding site for myosin head Forms a Cross-Bridge when myosin binds to G-actin Five Actin proteins surround the myosin in 3-D pattern

Actin Tropomyosin Protein that covers over the myosin binding site on G-Actin Myosin head can’t bind to G-Actin, muscle relaxes If the binding site on G-Actin is uncovered by removing Tropomyosin then myosin and actin bind, muscle contracts

Actin Troponin C Protein attached to Tropomyosin When Troponin C changes shape it pulls on Tropomyosin Calcium binding to Troponin C causes this protein to change shape Tropomyosin moves and uncovers the binding site on G- Actin, so Actin and Myosin can bind Contraction

Regulation of Contraction by Troponin and Tropomyosin Tropomyosin blocks myosin binding site (weak binding possible but no powerstroke) Troponin controls position of tropomyosin and has Ca2+ binding site Ca2+ present: binding of A & M Ca2+ absent: relaxation

Muscle Anatomy Sarcoplasmic Reticulum Terminal Cisternae Modified endoplasmic reticulum Wraps around each myofibril like a piece of lace Stores Calcium Terminal Cisternae Longitudinal tubules Transverse tubules (T-tubules) Triad-two flanking terminal cisternae and one t-tubule T-tubules are continuous with cell membrane

When Troponin binds calcium it moves Tropomyosin away from the actin-myosin binding site

Where does Calcium come from? Intracellular storage called Sarcoplasmic Reticulum Surround each myofibril of the whole muscle Contains high concentration of calcium Transverse Tubules connects plasma membrane to deep inside muscle

T-Tubules Rapidly moves action potentials that originate at the neuromuscular junction on the cell surface

Membrane depolarization or APs carried deep into the muscle by T-tubules Motor nerve T-tubule + Neurotransmitter receptors SR

My SR Ryanodine Receptor Dihydropyridine receptor T-tubule SR myoplasm

_ + _ + + + + _ _ + _ + _ + _ + _ + + Ca++ Ca++ Ca++ SR Ca++ pump Myoplasm (intracellular) _ _ _ _ + _ + + + _ + + _ _ + _ + T-tubule (extracellular) _ + _ + _ + +

Actin filament Binding sites Strong Weak binding binding Myosin head group S2 link Stretching of the link generates tension Myosin filament

Equal and opposite force Why do thin filaments move? Net force Net force Equal and opposite force on thick filament

Sliding Filament Theory When myosin binds to the binding site on G-actin muscular contraction occurs. The more myosin that bind to G-actin the greater the force of contraction Calcium must be present

Sliding Filament Theory Cross Bridge Myosin in the High Energy Configuration binds to G-Actin ADP + Pi are bonded to the myosin head when the cross bridge forms Power Stroke When the myosin and actin bind the myosin head changes shape Myosin pulls the actin and pulls on the Z-line Sarcomere shortens ADP+Pi no longer binds to myosin head

Sliding Filament Theory ATP binds to the myosin head Myosin changes to its Low Energy Confirmation In the Low Energy Confirmation Myosin breaks its bonds with Actin Rigor Mortis Lack of ATP Build up of Lactic Acid

Sliding Filament Theory ATPase ATP is hydrolyzed to ADP + Pi ATPase is on the myosin head Myosin changes shape back to its High Energy Confirmation

Sliding Filament Theory Some Myosin heads detach from Actin while other heads continue to keep their attachments No slipping of the Z-lines Contraction is held in place

What if we don’t have this? ATP X Actin + myosin  Actomyosin complex Rigor mortis

Events at Neuromuscular Junction Converts a chemical signal from a somatic motor neuron into an electrical signal in the muscle fiber

Events at Neuromuscular Junction Acetylcholine (Ach) is released from the somatic motor neuron Ach initiates an action potential in the muscle fiber The muscle action potential triggers calcium release from the sarcoplasmic reticulum Calcium combines with troponin C and initiates contractions

Events at Neuromuscular Junction Ach binds to cholinergic receptors on the motor end plate Na+ channels open Na+ influx exceeds K+ efflux across the membrane End-Plate Potential (EPP) EPP reaches threshold and initiates a muscle action potential

Events at Neuromuscular Junction Action Potentials move down the membrane K+ builds up in the t-tubules Depolarization occurs Calcium gates on the SR opens Calcium diffuses into the cytoplasm of the cell

Excitation-Contraction Coupling The process where muscle action potentials initiate calcium signals that in turn activates a contraction-relaxation cycle

Initiation of Contraction Excitation-Contraction Coupling explains how you get from AP in axon to contraction in sarcomere ACh released from somatic motor neuron at the Motor End Plate AP in sarcolemma and T-Tubules Ca2+ release from sarcoplasmic reticulum Ca2+ binds to troponin

 Net Na+ entry creates EPSP  AP to T-tubules Details of E/C Coupling Nicotinic cholinergic receptors on motor end plate = Na+ /K+ channels  Net Na+ entry creates EPSP  AP to T-tubules  DHP (dihydropyridine) receptors in T-tubules sense depolarization

Nicotinic Cholinergic Receptors

DHP (dihydropyridine) receptors open Ca2+ channels in t-tubules Intracytosolic [Ca2+]  Contraction Ca2+ re-uptake into SR Relaxation

Excitation-Contraction Coupling High cytosolic Calcium levels binds to Troponin C Tropomyosin moves to the “on” position and contraction occurs Calcium-ATPase pumps Calcium back into the SR The more myosin heads that binds to actin to stronger the force of contraction

Summary of events Synaptic Depolarization of the plasma membrane is carried into the muscle by T-Tubules Conformational change of dihydropyridine receptor directly opens the ryanodine receptor calcium channel Calcium flows into myoplasm where it binds troponin Calcium pumped back into SR

Neuromuscular Junction The more terminal boutons to attach to myofibers the greater the control of the muscle. Recruitment The greater the number of terminal boutons attached to myofibers there is more fine control of the muscle

Excitation-Contraction Coupling Twitch A single contraction-relaxation cycle in a skeletal muscle fiber A single action potential in a muscle fiber Latent Period Between the muscle action potential Time required for excitation-contraction coupling to take place

Is There Truth In Advertising? Is the banana company telling the truth when they claim that bananas being high in Potassium actually prevents or relieves muscle cramps? If so, how does this increase in Potassium relieve muscle cramps? If not, why not and how do we actually relieve muscle cramps?

Muscle Contraction and ATP Supply Phosphocreatine Backup energy source Quick energy used up in approx. 15 minutes

Causes of Fatigue Central Fatigue Subjective feelings of tiredness Arises in the CNS Psychological fatigue precedes physiological fatigue in the muscles Low pH may cause fatigue

Muscle Fiber Classification Oxidative only Oxidative or glycolytic Muscle Fiber Classification

Muscle Adaptation to Exercise Endurance training: More & bigger mitochondria More enzymes for aerobic respiration More myoglobin no hypertrophy Resistance training: More actin & myosin proteins & more sarcomeres More myofibrils muscle hypertrophy

Causes of Fatigue Peripheral Fatigue Arises between the neuromuscular junction and the contractile elements of the muscle Ach depletion, neuromuscular junction receptor loss Myasthenia Gravis

Skeletal Muscle Types Fast-twitch muscle fibers (type II) White Fibers Low Myoglobin Develops tension two to three times faster than slow-twitch fibers Splits ATP more rapidly to complete contraction faster Fatigues quickly

Skeletal Muscle Types Slow-twitch Muscle Fibers (Type I) Red High Myoglobin levels Slow to Fatigue

Contractions Isometric Contractions Isotonic Contractions Creates force without movement Isotonic Contractions Moves loads

Cross bridge Power stroke Working stroke Force stroke During skeletal muscle contraction the binding of the myosin head to G-actin occurs at which step? Cross bridge Power stroke Working stroke Force stroke

During the cross bridge the myosin head is in the ____ configuration. Low energy High energy Medium energy Power energy

Name the connective tissue layer that surrounds a fascicle in skeletal muscle. Endomysium Epimysium Perimyseum Tendon Epicardium

Name the functional unit of skeletal muscle. Sarcolemma Saroplasmic Reticulum Sarcomere Myosin

The thick filament is also referred to as Actin Myosin Tropomyosin Troponin C G Actin

Which protein in G-Actin is responsible for blocking the bind site of myosin? Tropomyosin Troponin C Sarcoplasmic Reticulum Sarcolemma

During skeletal muscle contraction Calcium is stored in the Sarcolemma Sarcomere Sarcoplasmic Reticulum Golgi Apparatus Transverse Tubules

The build-up of potassium in the _______ causes the resting membrane potential of skeletal muscle to depolarize. Sarcolemma Sarcoplasmic reticulum Transverse tubule Tropomyosin

Which enzyme is located on the myosin head? ATP synthase ATP ase ATP reductase Phophodiesterase Oxidase

During cross bridge formation myosin will bind to ________. Troponin C Tropomyosin G-Actin Myosin

The phenomenon of rigor mortis is a direct result of The breaking of myosin bonds by ATP The breaking of actin bonds by ATP The inability of the myosin cross bridges to combine with single amino acids The loss of ATP in dead muscle cells