Muscle Cell Physiology

Question 1

Skeletal muscle and skeletal muscle cells

Answer 1

Formed by fusion of embryonic muscle cells (myoblasts) = muscle fibers. Its inner part is densely packed with myofibrils (thin cylindrical structures)- 80% of its mass, and consists of myofilaments: actin + myosin. Myofilaments are organized in a repetitive pattern: smallest unit = sarcomere.
Each sarcomere contains 2 sets of actin filaments: 1 of them is anchored in a protein lattice -> dividing walls -> Z-discs (relaxed muscle => no overlapping)
Middle of sarcomere -> myosin filaments -> M-line, myosin ends => actin overlaps
Light bands: only actin (I-bands)
Dark bands: both (A-bands)

Question 2

Proteins in the sarcomere

Answer 2

• Titin: largest, ensures return of actin + myosin to their original position, O: Z-lines, I: myosin bundles
• Nebulin: stiff, rod-shaped, determines the direction + placement of actin polymerization, protects the developed actin, ensures that all actin filaments are the same length.
• Alpha actinin: net-like, provides binding site for the actin complexes.

Question 3

Actin

Answer 3

Globular actin molecules in a coiled double chain.
Main components: G-protein, tropomyosin molecule

When troponin complex binds to tropomyosin => tropomyosin slides into the groove of the 2 stranded actin helix => Cross-bridge cycle

Question 4

Myosin

Answer 4

2 heavy + 4 light polypeptide chains.
Heavy chains are twisted around each other -> “tail”, “neck”, “heads”. Heads are always pointing against the Z-discs and they can bind to the actin molecules + exert force on them by altering the angle bw the tail + heads => basis of contraction mechanism

Question 5

Electro-Mechanical coupling

Answer 5

Neural AP transferred to the muscle fivers => AP -> electrical signal reches the TRIAD (through T-tubuli) -> transformed into the calcium-signal => triggers response => contraction

1. Release of Ca
2. Activation of muscle proteins (Ca -> tropomyosin-troponin complex => acto-myosin complex)
3. Muscle contraction
4. Relaxation (Ca elimination: Na/Ca antiport mechanism)

Question 6

Fibers of muscle tissue

Answer 6

• “White”/ phasic muscles: fast twitch fibers, powerful contraction, anaerobic glycolysis (energy needs)
• “Red”/ tonic muscle fibers: slow twitch fibers, more sustained work, energy only from glucose oxidation
• Intermediate: intermixed, the reletive % determines the type.

Question 7

Energy sources

Answer 7

• ATP: contraction + relaxation, covers O2 needs for 2-3 sec.
• Creatine-P: energy reserve, intensive contraction
• Anaerobic GL: energy source in case of outstanding load (glycogen -> fast mvm, glucose -> long term contraction). If more ATP is used => O2 debt, accumulated lactic acid inhibits contraction at sarcomere.
• Oxidative phosphorylation: very-long term muscle activity (red)

Question 8

O2 debt

Answer 8

Cover energy needs by anaerobic GL, resynthesize previously depleted stores after work by consumption of O2 (under aerobic conditions)

Question 9

Macroscopic events- Elements

Answer 9

Amongst CC / sarcomere, SEC, PEC. First the SEC reach equilibrium with load, because of the contraction of CC (no mvm, only tension).

Question 10

Twitch

Answer 10

Appropriate stimulus => contraction: muscle twitch occurs (=single contraction-relaxation cycle). AP is not directly followed by a calcium transient: latency derived from the latency of measuring instruments / real biological latency.
Virtual latency: sum of 2 latencies

Question 11

Types of contraction

Answer 11

Isometric contraction: tension changes, length remains, muscle lifts a heavy load
Isotonic contraction: const tension, muscle is shortened
Auxotonic contraction: muscle shortens, increased tension, muscle works against a spring
Preload: after stimulation, 1 stretch SEC -> equilibrium -> contraction, shortening of muscle
Afterload: block the free mvm with a frame => no more shortening, but u can increase tension: isotonic -> isometric

Question 12

Summation

Answer 12

It’s the addition of skeletal muscle contraction forms.
▪️All-or-none: adequate stimulus => max, smaller stimulus => NO response
▪️Quantal summation: addition of elementary units -> increase of tension => more frequent AP
▪️Contraction summation: repetitive stimulus => increased contraction of prev Ca transient. If there is additional Ca release, may not be complted => amplitude of contraction increases
▪️Staircase effect (treppe): new stimuli after the end of a twitch => new contractions + increased amplitude (by IC Ca -> warming up)
▪️Tetanus: stimuli with increasing frequency => max contr state

Question 13

Length-Tension diagram

Answer 13

1. Passively stretch the muscle to A, B, C distances (L0 Isotonic max curve.
2. NO shortening, measure tension => Isometric max curve
3. Conduct the experiment (preload conditions) => preload max curve
4. ———” “———- (afterload conditions) => afterload max curve

Question 14

Work

Answer 14

Outer + Inner work. Estimation of the total work by the O2 consumption of the muscle. Wt = Wo + Wi
Efficiency= Wo / Wt ~20%

Question 15

Heat production

Answer 15

▪️Resting: production of heat => considerable ratio of basal metabolic rate
▪️Initial: beginning if contraction- Activation => electrochemical coupling, Contraction => most of initial heat
▪️Restitution: fast muscle generates energy by utilizing its energy stores. Resynthesis of the stores => heat production

• In white fibers: Initial heat -> Restitution heat, muscle “pays back” its O2 debt -> resynthesis of energy reserves
• In red fibers: after short initial glycolytic phase -> long lasting oxidative period, muscle is NOT exhausted, NO debt

Question 16

Power

Answer 16

Velicity- Tension diagram: small tension => high velocity, high tension => low velocity.
Optimal position: Intermediate load

Question 17

Fatigue

Answer 17

Ratio of glycolytic + oxidative fibers of the muscle. Caused by decrease of twitch amplitude + increase of twitch duration

• Physiological conditions -> NO, because of the increasing [metabolic by-products] => inability of [] in muscles.
• Vitro fatigue: after fatigue -> faster restitution, N-rich environment => unrecoverable fatigue state
• Vivo fatigue: Peripheral fatigue- decreasing energy stores, increasing [by-product], direct effect of lactic acid

Subjective feelings: increased heat production, decrease of pH, dehydration, hypoglycaemia

Question 18

Muscle-Nerve connection

Answer 18

• Trasnmission of neural AP -> muscle (myoneural junction)
• AP (n.terminals) => Ach release -> nicotinic receptors of muscle membr => opening of ligand cationic channels
  => end plate potential (EPP) gradually decreasing -> conformation change => AP

Question 19

Acetylcholine (Ach)

Answer 19

Transforms a neural signal (AP) to muscular electric signal (AP)
▪️Presynaptic area: AP (from axon), neural AP (Ca -> synaptic end) => Ach vesicle release.
▪️Synaptic cleft: filled with Ach
▪️Postsynaptic area: Ach -> receptors in myolemma => opening of ion channels -> EPP => activation of voltage Na channels => formation + propagation of AP.

• Nicotinic Ach receptor (muscle): 2α, 2β, 1δ => competitive blocking effect of curare + bungarotoxin.
• Nicotinic receotir (CNS): NO δ => more resistant to curare

Question 20

Motor neuron

Answer 20

Nerve + Muscle (supplied by this nerve)

• Large: speed = fast, fibre length = very long, fatigues
• Small: speed = slow, NO fatigue, fibre length = short

Question 21

Smooth muscle

Answer 21

3% of body mass.

• Single-unit: connected by gap junctions -> synchronized contractions (sustained -> transfers P to other organs, alternating -> mixing of content), waves of contr = peristaltic mvms.
• Multiple-unit: NO gap junctions => independent contraction, adjusting pupils’ diameter, altering curvature of the lens.

1 nucleus, actin + myosin (longer), intermediate filaments don’t participate in contraction -> shape of the cell, cytoplasm: actin filaments (bw them -> myosin)- dense protein lattices = Z-discs, NO T-tubules, sarcoplasmic reticulum = poorly developed

Question 22

Contraction in smooth muscle

Answer 22

1. Stimulation of cells => increased [Ca] (due to influx)
2. Ca-calmodulin: activation of myosin kinase -> transfers a P group from ATP -> myosin heads => phosphorylated => hydrolyze ATP + bind to actin.
3. Cross-bridges are formed + broken as long as the myosin heads are phosphorylated => cell contraction
4. Stimulation of the cell => more Ca is removed than flow in => [Ca] falls + Ca dissociates from the complex => activation of myosin kinase ceases
5. Dephosphorylation of myosin heads (myosin phosphatase) => NO ability to bind to actin => muscle cell relaxes.

Myosin-Actin: ATP contsumption (isometric contraction) = low, because of ATP hydrolyzation
Relaxation of smooth m = vasodilation
Extension of smooth m = contraction (Bayliss effect)