Physio. Ch.12 Muscles

Intercalated discs

• Junctions between cardiac muscle cells

• Allows cardiac muscle cells to contract as one unit

Triad

• Unit of a muscle

• Made of T tubule + terminal cisternae

Transverse (T) tubule

• Continuous with sarcolemma and penetrate into muscle fiber

Sarcolemma

• Transparent tubular sheath that surrounds the fibers of skeletal muscles

Terminal cisternae

• Enlargements of sarcoplasmic reticulum, store Ca

Neuromuscular Junction

• Excitatory synapse between neuron and skeletal muscle

• Comprised of

- Synaptic bulb of motor somatic neuron

- Synaptic cleft

- Motor end plate

• NT used: ACh

• Receptor used: Nicotinic

Motor Unit

• A single motor neuron and all the muscle fibers it innervates

- Average 200 muscle fibers innervated by 1 neuron

• Acts as a single functional unit

• Types

- Small: few muscle fibers per motor neuron, used when fine muscle control needed

- Larger: high number of muscle fibers per motor neuron, used when large amounts of strength needed

Graded contractions

• Varied contraction strength due to different numbers of motor units being stimulated

Sarcomere

• Functional unit of muscle

• Made of

- Thin myofilaments

- Thick myofilaments

- Titin filaments

- Cross bridges

- Z discs

- A band

- H band

Thin filament

• Made of

- Actin: Building block

- Tropomyosin: Covers binding sites on actin

- Troponin complex: Moves Tropomyosin off of binding site

Thick filament

• Has a bare sight in the middle of the filament

• Made of

- Myosin: Building block

- Tail: Sight for myosin on myosin binding

- Head: Holds ATP and actin binding stie

- ATP site: Acts as binding sight for ATP

- Actin binding sight: Acts as binding sight for actin

Sliding Filament Model

• Model of muscle contraction

• Muscle contracts through filaments sliding past one another

- Thin filaments pulled towards middle of sarcomere, the M line

• Powered by The Crossbridge Cycle

The Crossbridge Cycle

• Cycle that powers sliding filament model

- Step 1: ATP binds to myosin causing myosin and actin unbind

- Step 2: Myosin turns ATP into ADP and phosphate, storing both

- Step 3: Myosin is in it’s high energy form and cocks back

- Step 4: Myosin and actin bind together

- Step 5: Phosphate is released from myosin which causes a power stroke

- Step 6: ADP is released

- Step 7: New ATP binds to myosin head

Excitation

• Stimulation of a Muscle Fiber

• Step 1: AP gets to motor neuron and causes the resale of ACh

• Step 2: Nicotinic receptors receive ACh

• Step 3: End plate potential generated, will always reach threshold

Excitation-Contraction Coupling

• The sequence of events that links the action potential in a muscle cell to its contraction

• T tubules and SR membranes are physically linked through DHP receptors and Ryanodine receptors

- Action potential in T tubules is able to affect Na channels in SR

DHP receptors

• Receptors responsible for linking sarcolemma and t tubule

• Located in T tubule

• Connected to Ryanodine receptors

Ryanodine receptors

• Receptors responsible for linking sarcolemma and t tubule

• Calcium channel located in sarcolemma

• Connected to DHP receptor

Calcium in muscle contraction

• Bind to troponin complex

- Configuration changes, moving tropomyosin off of myosin binding sights

• Ca must be actively transported back into sarcomere

Relaxation

• Motor neuron stops stimulating muscle cell with action potential

• Ca is actively transported back into the sarcolemma

• Troponin and tropomyosin move to original positions, covering myosin binding sights

Muscle Twitch

• Mechanical response of an individual muscle cell, motor unit, or whole muscle to a single action potential

• Reproducible, all or nothing event

• Varies from cell to cell

• Phases

- Latent period

- Contraction phase

- Relaxation phase

Latent period

• Phase of a muscle twitch

• Delay between the muscle cell’s AP and the beginning of muscle contraction

• Causes by events of excitation-contraction coupling needing to be done

- Calcium release & binding to troponin

Contraction phase

• Phase of a muscle twitch

• Time when muscle tension/force is increasing

• Cross bridge cycle happens in this time

Relaxation phase

• Phase of a muscle twitch

• Time when muscle tension decreases back to zero

• Ca2+ actively moved back into sarcolemma

Isotonic contraction

• Muscle generates a constant tension just greater than any forces opposing it

• Tonic” = tension

• Subdivided into two forms

- Concentric

- Eccentric

Concentric

• Type of Isotonic contraction

• Muscle length shortens

Eccentric

• Type of Isotonic contraction

• Muscle length increases

Isometric contraction

• Muscle creates tension but maintains the same length

• “Metric” = length

• Load is slightly greater than force of muscle contraction

Force Generated by a Muscle

• Determined in a muscle by the number of muscle fibers contracting

• Determined in an individual fiber by number of myosin binding sites on actin that are exposed (active crossbridges)

- Frequency of stimulation determines number of active cross bridges

- Fiber diameter determines number of active cross bridges

- Changes in fiber length determines number of active cross bridges

Frequency of Stimulation

• Rate of calcium release into cytosol exceeds rate of active transport back into SR

- More exposed myosin binding sites on actin allowing more crossbridges formation

Summation

• Twitches add together when a muscle is stimulated at a high frequency

• Causes by multiple AP arrive before twitch complete

Tetanus

• Peak summation, maximal sustained contraction

• 4x to 5x stronger than a twitch

• Subdivided

- Incomplete Tetanus

- Complete Tetanus

Incomplete Tetanus

• Brief periods of relaxation between twitches

- Peaks are when calcium levels saturate troponin

Complete Tetanus

• A smooth, sustained contraction, no relaxation exist

- Enough calcium to continuously saturate troponin

Fiber Diameter

• The diameter of a muscle fiber

• Larger = more sarcomeres arranged parallel to one another

• Creates a greater force

Changes in Fiber Length

• Effects the force produced by one fiber

• Optimal ranges between 100 and 120

- Muscles try to operate in this range for as long as possible

Regulation of Muscle Force

• Amount of active motor units

- Primary way muscle force is regulated

• Recruitment: act of increasing the number of active

  motor units

Muscle cell energy generation

• Constant ATP needed for muscle contraction

• Sources of ATP

- Oxidative phosphorylation of ADP in mitochondria

- Phosphorylation of ADP by creatine phosphate

- Anaerobic glycolysis

Oxidative phosphorylation of ADP in mitochondria

• Main source of ATP production

• Fueled by glucose from muscle/liver or by fatty acids

Phosphorylation of ADP by creatine phosphate

• Secondary source of ATP production

• Transfer of a high-energy phosphate to ADP

• Active when muscle at rest

• Can supply 40 ATP, 5x the normal 8 ATP stored in a muscle

• Creatine produced by the liver and kidneys or obtained in the diet

Law of mass action

- Use of ATP drives the reaction to the right

- At rest, creatine phosphate is replenished

Anaerobic glycolysis

• Secondary source of ATP production

• Turns pyruvate to lactate

Light exercise energy production

• Oxidative phosphorylation

Moderate & heavy exercise energy production

• Cells first use up glycogen stores

• Then use blood glucose (first ~30 minutes)

- As exercise intensity and duration increase, more GLUT-4 transporters are inserted into the sarcolemma

• Then fatty acids

• Anaerobic glycolysis is especially important in heavy exercise (pyruvate buildup is converted to lactic acid)

Classification of Skeletal Muscle Fibers

• Two major categories

- Speed of contraction: time to reach peak tension

- Primary mode of ATP production

Speed of contraction

• Classification of skeletal muscle fibers

• Reffers to time to reach peak tension

• Subdivided

- Slow switch: slow myosin

- Fast twitch: fast myosin

Primary mode of ATP production

• Subdivision used to classify Skeletal Muscle Fibers

• Subdivided

- Glycolytic

- Oxidative

- Myoglobin

Glycolytic

• Fibers that primary energy source is this have high concentrations of glycolytic

  enzymes (glycolysis), few mitochondria

Oxidative

• Fibers that primary energy source are high in mitochondria concentration and capillaries

- Low low concentrations of glycolytic

- Contain myoglobin

Myoglobin

• Oxygen binding protein

Major Types of Muscle Fibers

• Slow oxidative

- slow myosin + produce most ATP by oxidative phosphorylation

- small diameter

• Fast glycolytic

- fast myosin + produce most ATP by glycolysis

- large diameter

• Fast oxidative (rare)

- ‘fast’ myosin + produce most ATP by oxidative phosphorylation

- Intermediate diameter

Muscle Fatigue

• Decline in a muscle’s ability to generate force

• Causes

- Depletion of stored glycogen

- Lactic acid accumulation (lowers pH → altered enzyme

activity)

- Interruption of blood flow due to strong contractions

- Accumulation of extracellular K+, reducing membrane

potential

- Neuromuscular fatigue: depletion of synaptic terminals of

ACh

- Fatigue of upper motor neurons in the CNS (Central fatigue)

Cardiac Muscle Cells

• Seen in heart

• Involuntary control

• Striated like skeletal muscle

- Use sliding filament method like skeletal muscle

• Connected by intercalated discs

• Has gap junctions

- Allowed electrical synapses

Electrical synapses

• Gap junctions allow AP to travel through entire cell network

• Muscle fibers contract as one unit

• Long AP durations stops summation when not wanted

• Pacemaker controls how many AP are sent out

Smooth Muscle Cells

• Involuntary control

• Regulated by ANS

• Short cells with one nucleus

• Nonstriated, no sarcomere

- Contraction occurs along several axes

• Electrical synapses present

Smooth Muscle Contractile Apparatus

• Myosin filaments are stacked vertically and can form cross bridges with actin

• Entire thick filament covered with myosin heads

• Myofilament arrangement allows contraction even when greatly stretched

Excitation-Contraction Coupling Mechanism in Smooth Muscle

Step 1: Depolarization causing Voltage-gated Ca2+ channels in PM and SR open.

intracellular calcium level raise

Step 2: Calcium binds to calmodulin causing a conformation change

Step 3: Activates myosin light chain kinase (MLCK)

Step 4: MLCK phosphorylates myosin light

chains activate Myosin crossbridges and Crossbridge cycling starts

Step 5: Muscle contracts

Smooth Muscle Relaxation

• Relaxation when Ca is pumped out by the ATP pump

• Myosin phosphatase dephosphorylation myosin

Regulation of Smooth Muscle Contraction

• Done by NE, ACh, paracrine or stretching of cell

• Regulated by both branches of ANS

- Effects of either branch may be excitatory or inhibitory

Single-unit smooth muscle system

• Multiple gap junctions that allows cells behave as a unit

• Most smooth muscles

Multiple-unit smooth muscle system

• Few or no gap junctions → cells require individual nerve innervation