Skeletal Muscle

Physiology 534 with Stephenson at Michigan State University

About this deck

By: Lauren Hasler
Textbook:

Histology: A Text and Atlas: With Correlated Cell and Molecular Biology (Histology (Ross))

Langman's Medical Embryology, Eleventh Edition: North American Edition

Medical Physiology: Principles for Clinical Medicine (MEDICAL PHYSIOLOGY (RHOADES))
Created: 2010-11-19
Size: 72 flashcards
Views: 37

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= epimysium

-penetrated by major nerves and vessels:

1. Axons of α, γ motor neurons

2. axons of proprioceptors to send into to CNS

= perimysium

-Contains smaller blood vessels and nerve: vascular supply depends on work rate of muscle and nerve density related to motor control (fine vs. gross movements)

= endomysium

-includes reticular fibers, ECM, basal laminae

-contains capillaries: density ↑w/ ↑ increased muscle usage

muscle fiber organization

Biggest → smallest

1. Myofibril = bundles of proteins inside each muscle fiber

2. sarcomere: functional unit of muscle

3. myofilaments: thin(actin) and thick (thick) moving contractile proteins

4. Anchoring proteins" provide structure to muscle cell

Muscle characteristics

Multinucleated arranged along cell periphery
Striated due to alternating pattern of myofilaments
Basal lamina surrounds each muscle cell, synthesized by myoblasts and satellite cells
Contractile properties along myofilaments
Pennation angle may be // or at an angle to the line of force development
Muscle fiber length
Musculotendinous junction at terminal expansion to increase surface area

motor neuron

= α motor unit form ventral horn, efferent intervention needed for muscle fiber survival

Motor unit

= α motor unit + all innervated fibers

-Extrafusal fibers are innervated fibers responsible for force generation

-Muscle fibers of different motor units are intermixed within a fascicle

Proprioceptors

Send info about muscle length and force changes to CNS (afferent innervation)

-golgi tendon organs @ junstion b/w muscle fibers and tendons/aponeurosis

-Muscle spindles w/in perimysium

what types of organelles are in skeletal muscle fibers?

- mitochondria

-multiple nuclei: regulate activities

- developed smER = sacroplasmic reticulum, for Ca++ storage

Satellite cells

i. Stem cells w/in the basal lamina

ii. Can divide or fuse w/ muscle fibers à larger muscle fibers

iii. Important for muscle repair and regeneration

iv. origin unknown but may be derived from myoblasts that never fused to myotubes

Neuromuscular junction

-One NMJ per muscle fiber located in the middle of the fiber

- ACh receptors concentrated at motor end plate

Muscle spindles

= Spindle shaped CT enclosing specialized muscle fibers and sensory endings, responsible with the afferent neurons for the fine movement muscles = reflex

1. intrafusal fibers: nuclesase bag and nuclear chain fibes,

2. γ motor efferent neurons innervate intrafusal fibers to contract

3. intrafusal fibers are innervated by type Ia and II afferent nn: Muscle stretch → distortion of axon terminals → depolarizations → APs

4. spindle density: fine movement > gross movement muscles

Golgi Tendon Organs (GTO)

= sensory receptor that responds to tension with info relayed back to the spinal cord by Ib afferent nerves

1. Axon terminal embedded in collagen of tendon:Collagen stretch → distortion of axon terminals → depolarizations → APs

2. Role in exciting antagonist muscles

3. ~ 1 GTO/ 10-15 motor units

4. Located in the musculotendinous junction

Trophism

= communication b/w the motor nerve and skeletal muscle

a. Mutual exchange of trophic factors b/t muscle fibers and motor neurons

b. Innervations is required for normal muscle function

c. Motorneuron dictates fiber type characteristics

d. Severing α motor neuron(spinal cord injury) → denervation atrophy

e. loss of activity in the muscle → death of α motor neuron= disuse atrophy

f. Reattaching a new motor neuron reprograms muscle fiber to the new type

Embryonic development

a. Embryonic mesenchymal cell → embryonic myoblast→ myotube → myofiber ( mature cel)

b. Myoblasts begin synth actin and myosin which fuse to form myotube

a. Myotube

i. Central nuclei

ii. Synthesize the rest of contractile proteins

iii. Arranges into myofibril

i. Muscle cell plasma membrane

ii. Voltage-gated Na⁺ channels → excitable

iii. AP conduction similar to unmyelinated axon

iv. Invaginate into T-Tubules (confluent w/ ECF) that spread depolarization throughout muscle quickly

-Stores Ca++ and released with an AP in the t-tubule

-Bubbling near T-tubules = Cisterna

-Triad = the cisterna of 2 adjacent collars + 1 T-tubule

= ordered arrays of contractile filaments and anchoring proteins forming a cylinder

-each one surrounded by SR, mitochondria, and glycogen

-arrangement ensures contractile proteins are close to Ca++ and energy sources

-functional unit = sarcomere

-Contraction = shorteneing of sarcomere = myofibril shortens

-~ same length for all muscles = ↑ sarcomere number if loner muscle fibers

-myofilmants = actin and myosin

-specialized proteins hold structure together

-Anchored @ Z-line by α-actinin and nebulin

1. Primarily composed of globular actin strung together to form f-actin (filamentous)

2. Bound to regulatory protein complex :

-Tropomyosin: lies in the grooves of the helical actin polymer to help support it

-Troponin: binds to tropomyosin, 3 subunits

a. Tn-T: tropomyosin binging subunit

b. Tn-C: Ca++ binding subunit

c. Tn-I: inhibitory subunit

- anchored in center @ M-line where there are only myosin tails by myomesin and C protein

-each molecule has 2 heads joined by flexible links to a single tail

-each head has 1 actin binding site and 1 ATP binding site

-myosin + actin = ATPase

Troponin/tropomyosin regulation of actin/myosin binding

1. sarcomere at low Ca++ = tropomyosin blocks the myosin binding site of actin = muscles relaxed

2. sarcomere at high Ca++ = Ca++ binds to Tn-C → conformational change in troponin-tropomyosin complex → troponin no longer blocks the binding sire to myosin → muscles contracted

titin

1. largest known polypeptide

i. Extends from Z-line to M-line

ii. Spring-like structure

iii. Elastic regions which allow passive tension of muscle

iv. Regulates myosin assembly into thick filaments

What links sarcomeres to eachother?

= Desmin and dystophin

-Desmin: intermediate filament that forms a lattice around the myofibril that link Z-disks of adjacent myobifrils so they remain in line (Genetic disorders result in progressive myopathy (muscle fiber damage and weakness)

- Dystrophin: anchors structural actin to integrin glycoproteins of cell membrane (which are linked to basal lamina) to link the shortening or force of thin/thick filaments to the sarcolemma and ECM

Duchenne muscular dystrophy

= X-linked disorder where dystrophin is absent = muscle fibers lack structural stability

-muscle fibers are damaged during contraction → atrophy/cell death

-muscles ↑ in fat and CT cells

-weakness is progressive

-affects smooth and cardiac muscle too

Other muscular dystrophy diseases

(a) Becker’s muscular dystrophy – have less and/or dysfunctional dystrophin

(b) Dystrophy involving sarcoglycan complex of sarcolemma – LGND

hypertrophy

= muscle growth

i. Occurs by increasing number of myofibrils and myofilaments

ii. Under given stress – loaded

iii. Requires IGF-1 Activation – IGF-1 relased from danaged muscle fibers → activates satellite cells and cause them to fuse with muscle fiber → enter cells and work to repair area of muscle

What inhibits extensive growth of muscle tissue?

= myostatin

(a) Can have myostatin resistance or no myostatin production

(b) Children have very large muscles – even twice the size of normal

Hyperplasia

= increased cell number by division and fusion of satellite cells

- not strong evidence for this

Atrophy

= decreae ub muscle fiber number and isze

reasons:

1. Dissuse atrophy

2. Denervation atrophy

3. Aging: muscle fiberes ↓ in sixe and number → replaced with CT

reinnervation

after denervation motor neuron axons may grown back

-new end plate, new motor units (larger and not in mosaic pattern)

-sensory axons may grow back too but can be incomplete and inappropriate

Cross-bridge cycle steps 1 and 2

1. Attachment (rigor): myosin and actin bound, ATP needed for myosin and actin to release from eachother

2. release: ATP binds to myosin→ conformational change of myosin at actin binding site → myosin then has ↓ affiinty for actin → myosin released from actin

Cross-bridge cycle steps 3 and 4

3. Hyddrolysis/Bending: ATP → ADP + Pi bound to myosin → conformation change of ATP binding site of myosin →myosin head bends toward Z-line

- muscle at rest (low Ca++)

4. Power stroke: ↑ Ca++ →myosin-ADP-Pi binds weakly to actin → ADP+Pi released → myossin-actin more tightly bound and myosin moves toward m-line

= force generating step of cycle = where shortening occurs

Cross-bridge events

-each cycle of cross-bridge formation = 1 APT

-each thick filament has 200-300 myosin heads, all cycling and using ATP

cycle rate limited by the ATP hydrolysis rate of myosin

- more sarcomeres inseries = more shortening

Excitation contraction coupling (ECC)

= coupling the depolarization of the muscle fiber that leads to a mechanical response

-neural AP (ACh relased with ↑ [Ca++] at axon terminal) → motor end plate depolarized (nicotinic cholinergic receptors open) → mixed potential → muscle fiber AP down sarcolemma → activate voltage sensing channels w/in T-tubules (dihydropyridine receptor- DHPR) → Conformational change in Ca++ channel receptors (ryanodine-RYR) on SR → Ca++ release into cytosol → cross-brindge cycling → contraction

Ca++ concentration in cytosol

1. rest = low b/c srored in SR away from myofiliaments

2. higher Ca++ = binds to TnC → conformational change → tropomysoin moved from myosin binding sites of actin

3. Ca++ high enough = cross-bridge cycling until as long as Ca++ maintained (CBC controlled by controlling Ca++ levels with release and reuptake from SR)

4. max force = 10 μM Ca++ and relaxation = 0.1μM Ca++

muscle activation = all or none

-AP in motor axon always releases enough transmitter to depolarize muscle fiber above threshold

- ACh rapidly degraded in synaptic cleft + hyperpolarization after each AP = only 1 muscle AP in response to 1 motor axon potential

-1 motor neuron = AP in all the muscle fibers within its motor unit = all mucle fibers in a motor unit contracct at the same time

Ca++ATPase

immediately after release, CA++ is taken up again by SR against concentration gradient

-Ca++ATPase affinity > troponin

-pump activated by ↑ cytosolic [Ca++]

-Ca++ binding proteins inSR = calsequestrin: help ↓ the effective gradient that Ca++ pump works against

active state time period

- AP = 2-4 ms

-[Ca++] = 40-80 ms

-Twitch force = 100-200 ms

fibrillation

= spontaneous contraction of a muscle fiber, can be recorded with EMG

-cause: denervated muscle fibers initially depolarize at MEP

Fasciculation

= firing of a motor unit

-normal or in absence of peripheral neuropathy

Lidocaine

= blocks Na++ channels = blocks neuron AP = blocks entire ECC

Myasthenia Gravis

= decreases/blocks ACh receptors = reduced MEP potential → muscle fiber AP blocked if threshold not reached

what is the result of blcoked SR Ca++ reuptake?

= prolonged cross bridge cycling = longer contraction

Botulinum toxin (Botox)

= blicks Ach release = no MEP potential → rest of ECC blocked

dystrophin defect effects what?

= reduced muscle fiber shortening or force

what is the RYR-DHSR pathway analogous to?

= IP3 receptor pathway that induces Ca++ release form organelles in other cell types including sm. muscle

What is the result of ↑ external [Ca++]?

= ↑ [Ca++] gradient → influx of Ca++ → ↑ transmitter release

-NO effect on Ca++ release by SR b/c related to membrane potential of the t-tubule and the cytosol, not external [Ca++]

types of contraction

1. isometric = muscle develops force or tension but can't shorten

-cross-brindges form but the force produced matches the load

2. concentric = muscle develops force and shortens

3. eccentric = muscle develops foce and lengthens

what is the clinical importance of eccentric contractions?

1. muscle strengthening ↑ w/ eccentric contractions exercises

2. powerful eccentric contractions can lead to substantial muscle damage = soreness and injury

levers

1. 1st class = fulcrum b/w resistance (head) and effort (neck extensor muscles) (ex: atlanto-occipital joint w/ extension)

-E-F-R

2. 2nd class= resistance b/w fulcrum and effort (plantar flexion)

-F-R-E

3. 3rd class = effort b/w fulcrum and resistance (elbow joint flexion)

-F-E-R

total force (tension) depends on what?

= starting length

-total force = passive (resistance to stretch) + active tension (CBC)

twitch

= contraction: muscle develops force then relaxes with applied electrical stimulus

Contaction time

= time to reach peak force

-reflection of the cross bridge kinetics and elastic properties

relaxation

1/2RT = time requires for the muscle to return to 1/2 its resting force

-Ca++ATPase determine this rate

length-tension relationship

-the peak tension changes at different lengths with an isometric contraction

-maximal force = when all of the myosin head overlap with thin filament and can potentially bind to actin

-optimal length = length that allows max. cross bridge formation

-↑ overlap of thick and thin filaments = ↑ cross-bridges = ↓ sarcomere length = more force/tension produced

how does cross-sectional area affect isometric force?

change in number/sizeof myofibril = change in cross-bridges

-large muscle = large force

what is the primary source of muscle elasticity?

= titin, but CT also contributes (epi-, peri-, and endomyosium, tendon)

force-velocity relationship

= the greater the load the slower the shortening velocity

-the faster the rate of CBC → faster the rate of muscle shortening

-force-velocity curve: vmax and fmax inversely related

> eccentric contraction = force ≥ force with isometric contracition

Power

P = force developed X velocity of shortneing

-max power = 1/3 max force on force-velocty curve (where muscle if most efficient)

mooment arm

= distnace fromt he joint center to the muscle

-max = joint @ 90º

- decrease moment arm length by ↑ or ↓ 90º

- used to calculate Torque (NM) = force (N) x moment arm (m)

where are elbow flexors the weakest?

= extension b/c moment ar the shortest

myosin isoforms

1. type 1 = slowest cycling rate = lease amount of ATP/time, slow oxidative (SO)

- 1 mole ATP/min indefinatley, depend on aerobic metabolism

2. Type IIa = fast cyclying rate = more ATP/time, fast oxidative glycolytic (FOG)

- 2.5 mole ATP/min for 1-2 min, use both anaerobic and aerobic with lg. capacity for oxidative phosphorylation

3. Type IIx = fast cyclying rate = more ATP/time, Fast glycolytic (FG)

- 4 moles ATP/min for 10 sec., rely heavily of glycolysis

note: human muscle = mostly Type I and IIa

what is muscle's high-energy phosphate store?

= creatine phosphate: ADP + PCr (phosphocreatine) ↔ ATP + Cr (creatinine)

-enzyme = creatine kinase (CK)

-reaction = rapid → almost immediate source of ATP

How does PCr buffer ATP during exercise?

-Pcr level can drop by 90% durug a contraction whil ATP levels remain constant

- can be stored at much higher concentration than ATP

what reactions replensih PCr?

1. glyolysis

2. oxidative phosphorylation

muscle fiber structure stains with myosin isoforms

1. Type 1 = myoglobin, many mt., high capillary density, smaller fiber size, shorter diffusion distance, stain darker for NADH

2. Type IIa/IIx = larger diameter, fewer mt., less myoglobin, fewer capillaries, greater glycogen stores, and more extensive SR = rapid Ca++ handling

motor unit and muscle fiber type for each myosin type

motor unit:

-I = slow fatigue resistant

-IIa = fast fatigue resistant

-IIx = fast fatigable

Muscle fiber:

-I = slow oxidative (S)

-IIa = fast oxidative glycolytic (FOG)

-IIx = fast glycolytic (FG)

Change in motor untis

1. IIa ↔ IIx = yes

2. I ↔II = not likely

temporal summation

= increasing the force produced by the motor units by prolonging the Ca++ active state

-done by sending AP from motor neurons more frequently

- multiple AP can produce summation of twitch tension

-tetanus = max force that can be produce by temporal summation

- is possible b/c the refractory period of the sarcolemma is relatively brief compared to the duration of the contraction

spatial summation

= activating more motor units = ↑ force production: resulting tension for the whole = the sum of tension for each motor unit

- Henneman size principle = recruitment is orderly: Type I→ Type IIa → Type IIx because the cell body of the motor neuron for Type I motor units is smaller than Type II = lower threshold for AP

> allows precise level of force

how can force of a muscle be increased?

1. recruiting motor units = spatial summation

2. increasing the fifing rate of motor neurons for motor units once they are requited = temporal summation

3. optimal joint angle/length

4. Recruiting other muscles (synergists)

5. inhibiting opposing muscles (antagonists)