PNB Quiz 7 Skeletal Muscle

excitability

muscles generate graded and action potentials like a neuron

use action potentials to generate contraction

elasticity

muscles are constantly changing size

they have a resting length but they don’t lose membrane integrity when they experience large changes in size

muscle can be shortened or extended beyond resting length

functions of muscle

movement

posture - muscles contracted at all times

heat - produced when muscles contract which is important for temperature homeostasis

myocyte

mature muscles cells (also called muscle fibers)

multinucleated (3 or more nuclei per cell)

cylindrical shape

have striations

are densely packed

myocyte development

1) differentiation of multipoint stem cells called myosatellite cells

2) stem cells become immature muscle precursor called myoblasts

3) myoblast line up next to each other and form tube-like structure of a muscle cell

muscle organization

multiple level system of tubes within a tube

network of bundled fascicles held together by epimysium

fascicle

bundle of muscle of fibers that is held together by connective tissue wrapper (perimysium)

myofibrils

arrangement of contractile proteins inside a muscle fiberl

smallest tube in the system

myoglobin

oxygen binding protein

responsible for color of muscle fibers

counterpart of hemoglobin

type 1 fibers

darkest red → have the most myoglobin

good at binding and trapping oxygen

produce a lot of ATP and can stay contracted for long period of time

slow-twitch

ex: postural muscles and muscles used for endurance activities

type 2B fibers

little or no myoglobin

rely on anaerobic respiration

used for short bursts of activity like sprinting

fast twitch

type 2A fibers

some myoglobin

intermediate → little bit of aerobic respiration

fast twitch

myocyte structure

larger, thicker, and more cylindrical than most other cell types

as many myofibrils as possible

very little cytoplasm

mitochondria pushed to periphery of cell

sarcoplasm

the cytoplasm of a muscle cell

sarcolemma

the plasma membrane of a muscle cell

sarcoplasmic reticulum

the endoplasmic reticulum of a muscle cell

sarcomere

repeating units of contractile proteins

many of these in one myofibril

contract in an oscillatory manner like an accordion (ends move toward center)

myosin

thick filament or contractile protein in sarcomere

shaped like golf club

heads contain enzymatic domain that can breakdown or hydrolyze ATP into ADP and phosphate

actin

thin filament in sarcomere

each individual protein is a sphere (G actin)

when polymerized, individual proteins form long chains/filaments (F actin)

titan

tiny elastic protein in the sarcomere

sliding filament theory

thin filaments (actin) slide across thick filaments (myosin) towards the center of the sarcomere

shortness the H zone and the I zone

2 lines move closer together

A band does not change

on large scale will contract entire muscle cell

regulatory proteins

troponin and tropomyosin

present in same spots as actin and myosin

regulate contraction

cross bridges

binding between actin and myosin

must be formed for contraction to occur

tropomyosin

filamentous rope like protein

blocks myosin binding site on actin when there is a low intracellular calcium concentration

• cross bridges can’t form

troponin

smaller regulatory protein

made of 3 subunits that bind to different things

calcium binds here and will cause conformational change that allows it to move tropomyosin out of the binding site

• allows cross bridges to form

ATP

energy critical for contractile protein assembly and function

polymerizes G-acting to F-actin

forms cross bridges

cross bridge formation

1) ATP binds to myosin head and releases actin in existing cross bridges

2) Myosin ATPase hydrolyzes ATP into ADP and phosphate

3) ADP and phosphate stay bound to myosin head and myosin head twists to high energy conformation that binds to actin - cocked state

4) phosphate gets released so myosin head untwists into low energy state, pulling actin one position closer to center of sarcomere - power stroke

5) myosin releases ADP and binds to actin again

Calcium

cross bridge formation begins with this

binding physically impossible without it because tropomyosin is in the way

sliding of filaments can only repeat if these levels stay high

rigor mortis

stiffening of muscles and partial contraction once a person dies

body stops producing ATP after death

• cross bridges can’t be broken → muscle gets stuck in whatever state of partial contraction it was in

• concentration gradients breakdown, Vm depolarizes, and calcium in SR gets released into cytosol allowing new cross bridges to form

sets in fast and takes 18-36 hours for tissues to breakdown and for muscle to relax

useful for medical examiners to determine how long someone has been dead for

cold shortening

skeletal muscle contracts when cold to generate heat for the body

became problem in meat industry with invention of refrigeration because it turns meat into hockey pucks

• found out this could be prevented by shocking carcasses repeatedly at high voltages, depleting muscle fibers of calcium

Shows us that calcium needed for muscle contraction is released by electricity

neuromuscular junction

where neurons synapse with skeletal muscle fibers

motor neuron will fire action potential that releases neurotransmitters that stimulate muscle fibers to fire their own action potentials

every single muscle fiber is innervated by the axon terminal of the motor neuron

motor unit

single alpha motor neuron and the muscle fibers that it controls

must muscles contain multiple of these ranging in size

all or nothing principle

when motor neuron fires an action potential, ALL of the muscle fibers will also their action potentials

acetylcholine

specific neurotransmitter released by alpha motor neuron

finds receptors on plasma membrane of muscle fiber to bind with

motor end plate

part of the muscle fiber that synapses with the motor neuron

ACh receptor

ligand gated channel on motor end plate

cation ion channel

• when opened, Na and K can pass through

• major effect is that sodium can enter the muscle and create a graded potential

healthy muscle

action potential are always created because there is always enough ACh released to open up sufficient number of receptor channels

there are no sub-threshold stimuli

end plate potential

the graded potential created at motor end plate

diffuses away into different regions of sarcolemma to begin action potential

action potential

gets initiated in both directions and travels away from end plate, which is in the middle of the muscle fiber

Termination of signal

relies on diffusion of ACh out of synapse

or ACh esterase

• enzyme. that breaks down ACh in the synapse

curare

competitive antagonist that binds to ACh receptor

blocks binding of ACh

prevents all other steps of action potential

used in US for lethal injections

• ethical battle because it produces muscle paralysis without loss of consciousness

eserine

plant based inihbitor or ACh esterase

used to amplify synaptic transmission through NMJ because it increase time that ACh stays in synapse

crosses blood-brain barrier, so it can be used to treat nervous system disease

useful antidote to reverse effects of some types of sedatives

Succinylcholine

used to paralyze muscles before surgery

ACh receptor antagonist

• binds and activate ACh receptor

• mimics effects of ACh

can’t be broken down by ACh esterase, so it doesn’t allow for repeated signal transmission

myasthenia Gravis

autoimmune disorder hwere body produces antibodies that lead to destruction of ACh receptors

all or nothing principle goes out the window because people might not be able to produce enough end plate potential to start action potential

causes muscles to be fatigued more easily

• specifically ones that get used more often

symptom: droopy eyelids

Lambert Eaton Syndrome

mutation in VG calcium channels in axon terminal in motor neuron

decreases amount of ACh released onto motor end plate

causes muscle weakness and fatigue

Guillan Barre Syndrome

random rapid onset of muscle paralysis

autoimmune disorder that people describe as being locked inside their body

attacks glial cells that myelinate internodes of motor neuron

conduction efficiency through axon slows down and action potentials don’t always reach axon terminals → ACh doesn’t get released and muscle never gets stimulate

usually stimulated by immune response that body is having

people argue that vainness activate immune system and could cause this but odds are extremely low (have the same chance of getting it from the common cold)

sarcolemma

has very specialized structure

at surface of the cell and travels deep down into the muscle fiber to create a t-tubule

t-tubule

allow rapid exchange between interstitial fluid and deepest parts of muscle fibers

necessary because of small amount of cytoplasm in muscle fibers that limit diffusion of molcules

sarcoplasmic reticulum

extremely well developed inside of muscle

main calcium storage organelle where calcium is highly concentrated

releases the calcium needed for contraction

triad

feet of the SR meeting with each side of the T-tubule

DHP

voltage sensitive protein in T-tubule

RYR

calcium channel on SR

Excitation-contraction coupling

transduction of electrical signal into mechanical force

1) excitation - change in membrane potential created at NMJ

2) action potential leaves motor end plate and travels down each membrane segment of sarcolemma to enter the T-tubule

3) when action potential goes into T-tubule and changes MP around DHP, DHP changes conformation and pulls open the RYR, allowing calcium to move down concentration gradient into cytoplasm

4) filaments can now slide and contraction is created

relaxation

just as important as contraction

calcium goes back into the SR via the active transporter SERCA

• located on membrane of SR

• uses ATP to move calcium again gradient

calcium has to rest to resting levels

twitch

single contraction-relaxation cycle inside individual muscle fiber

longer delay before entering contraction phase

latent phase - when molecular events of coupling are happening (Ca getting out of SR)

first 5-6 msec

length tension relationship

muscle fibers have resting length, which is optimized for maximum tension generation

optimal length of the sarcomere

too much or to little overlap of actin and myosin results in decreased tension and decreased ability to generate force

• in a stretch muscle, cross bridges can’t really form and filaments can’t slide properly so low tension created

• in a shortened muscle, there is no room for filaments to slide because there is no room adjacent to M line for actin to slide over, which means muscle can’t generate a lot of force

summation

tension generated by skeletal muscle can be summed when stimulated at high frequency

single twitch only generates small amount of tension for short period of time, but repeated stimuli allows tension to build

in order for muscle to work properly, maximum tension much be reached in each fiber

as frequency of stimulation increases, fiber will go through tension building phase

unfused tetanus

tension building phase on a muscle fiber

tension is building unevenly

fused tetanus

frequency of stimulation becomes fast enough and can get up to maximal tension

when held in this contraction, it allows multiple muscle fibers to work together as a unit within a muscle

fatigue

muscles habe stayedi n tetanus for too long and become weak and lose ability to produce tension

depletion theory

• muscle fiber runs out of stuff to produce contraction (ATP and oxygen)

research done on how important proteins become less sensitive to calcium in this state

creatine

protein in muscle used to store ATP when there is a surplus

adds phosphate to protein so it converts to phosphocreatine, storing energy for later use

when muscle works hard, phosphate is removes and muscle can use the stored ATP

supplements of this are criticized because in order to make phosphocreatine, you need to have excess ATP and enzyme to make the conversion, sos just supplying the template might not do anything

supplements

cause tissues to become hypertonic and retain water

linked to weight gain

ex: creatine

whole muscle tension

not all muscle cells in a muscle contract at the same item

• only ones activated by same neuron

number of motor units that are activated determine the strength of contraction

small number of units = weak contraction

large number of units = stronger contraction

muscle tone

continued steady, low level of contraction that stabilizes joints and maintains general muscle health

% of fibers that are contracted at a given time

recruitment

stimulating more motor units to contract depending on need

• to generate more tension and increase force generated, more muscle fibers need to be brought to fused tetanus

lifting heavier objects → more motor units recruited and larger motor units recruited

Type 2B fibers recruited to generate greatest amount of force

dystonia

involuntary sustained muscle contractions resulting in twisting and receptive movements of abnormal postures

loss of muscle coordination and tone

ex: blaspharospasm: spasm of muscle surrounding tear duct in eye

Parkinson’s disease

severe dystonia that originates in brain

two forms: unwanted contraction and inability to contract when wanted

even when tremoring, if patient works really hard, they can still recruit motor units under voluntary control and overpower ones that are not working

treatment of dystonia

varies upon type of dystonia and severity

deep brain stimulation is very invasive so it is a drastic step reserved for severe cases (parkinson’s)

can be treated with drugs that target NMJ or Botox

botox

toxin effects snare proteins on presynaptic membrane that allow vesicle containing ACh to dock

• ACh can’t get releases

causes muscle paralysis

isotonic contraction

happen when there is a gradient between the amount of force generated by muscle and the resistance offered by object being moved

muscle fibers change in size

creates movement

force > load

isometric contraction

when muscles can’t generate enough force to move object

fibers can’t change length

tension develops from stretching of elastic proteins in sarcomere

load > force

A band

The entire length of the thick (myosin) filaments, including regions where they overlap with thin filaments

remains constant in length during contraction

I band

Region containing thin (actin) filaments only, with no thick filament overlap.

shortened during contraction

h zone

Central region of the A-band containing thick (myosin) filaments only, with no thin filament overlap.

shortens and can disappear completely during contraction

m line

Structural protein network running down the exact center of the sarcomere that anchors thick filaments.

stays in place during contraction

z line

The zigzag boundaries marking the ends of a single sarcomere; anchors the thin filaments.

move closer together during contraction