Muscle 1 - 3 Flashcards
skeletal muscle is responsible for:
voluntary movement of bones that underpin motion
control of inspiration by contraction of diaphragm
skeletal muscle pump - contraction of muscle helps with venous return to the heart
sarcomere is made of
actin and myosin filaments
sarcomere lines and bands (5)
during contraction:
Z line I band A band M band H band during contraction - I band shortens, A bands are fixed and stay the same
Z line
anchoring point for adjacent sarcomeres
I band
actin fibres
light
A band
mysoin and actin
overlapped - crucial for contraction
darkest
1 myosin for 6 actin filaments
M band
where myosin projects out
H band
just myosin
dark
why does skeletal muscle look striated
due to how muscle reacts to polarised light
intiating contraction
release of ACh at NMJ initiates action potential in plasma membrane
wave of depolarisation passes along sarcolemma and through t tubule network to reach interior of cell
in skeletl muscle, ER is specialised = sarcoplasmic reticulum
t tubule runs near 2 areas of SR forimg triad
depolarisation triggers an increase in intracellular calcium
number of muscle fibres stimulated depends on control needed
depolarisation travels through sarcolemma, along t-tubules and deep into cells
triad junction is between A and I bands
Cross bridge formation in muscles
- ATP dependant process
1 - rigid actin and nyosin are tightly bound, no ATP
2 - ATP binds to myosin head, changes tightness of binding, myosin head dissociates from actin
3 - ATP –> ADP + Pi, gives conformational change in shape of myosin head, ‘resting state’, extends limb
4 - head can interact with actins further down chain, it binds and forms weak cross bridge
5 - phosphate is released = strong cross bridge
6 - conformational change in myosin head, causes power stroke, myosin back upright and pulls on actin so filaments slide past each other
7 - ADP released, ready to start again - each thick filament contains approx 300 myosin heads
- each head cycles 5 times a second
summation of skeletal muscle
type = frequency
single muscle twitch = low frequency stimulation
temporal summation = inc freq before muscle has had change to relax (summation)
fused tetanus = contracted state is linked to recycling of Ca
contraction and relaxation is often slower than actual action potential
classes of muscle fibres (3)
slow oxidative = type I
fast oxidative = type IIa
fast glycolytic = type IIx/IIb
Slow oxidative muscle fibres - type I fatigue colour metabolism glycogen content ATP synthesis mitochondria muscles
resistant red oxidative low aerobic high soleus (slow twitch)
Fast oxidative muscle fibres - type IIa fatigue colour metabolism glycogen content ATP synthesis mitochondria muscles
resistant red oxidative abundant aerobic higher gastrocnemius (fast twitch)
Fast glycolytic muscle fibres - type IIx/IIb fatigue colour metabolism glycogen content ATP synthesis mitochondria muscles
fatiguable white glycolytic high anaerobic fewer biceps brachii
Comparison of muscle fibres
- type I
very resistant to fatigue
control posture e.g. calf muscle
relies on oxidative phosphorylation
advantage = can generate force for a long time, generates some force, slowly
Comparison of muscle fibres
- type IIa
for power running / walking frequency needed to get to tetanus is higher fatugues quicker rapid generation of force
Comparison of muscle fibres
- type IIx
biceps etc tires fastest rapid generation and rapid drop of force high freq for tetanus can't keep gneration of force for a long time
Slow vs Fast twitch fibres
slow fibres = half diamete of fast, take longer to contract after nerve stimulation
fast fibres = 10 miliseconds or less to contract
Neuromuscular junctions and inhibitors - muscle
calcium increase causes formation of vesicles so ACh can be released in synaptic cleft
depolarisation of axon = driven by Na channels, Na channels close, K channels open to bring mem potential back to resting
e.g. tetradotoxin inhibits Na channels = no depol = no action pot generated
e.g. dendrotoxin keeps membrane depolarised = continued release of ACh
mechanism of botulinum toxins
most common casue of food poisoning
muscle weakness - paralysis - death
symptoms = dry mouth, diarrhea, paralysis
cleaves SNARE complex required for exocytosis of ACh in ANS
cant fuse vesicles to membrane
ACh cant be released = paralysis
clinical use for botulinum toxin
treatment of cross eyes and uncontrolled eye movements
botox ( toxin A )
aerobic endurance training
sustained, low level exercise stimulation of slow fibres conversion of IIx into IIa increased fatigue resistance, blood capillaries no change in muscle strength
anaerobic endurance training
brief, intense exercise e.g. weight lifting
stimulation of fast fibres
no change in number of muscle fibres
enlargement of myofibril size by addition of new myofilaments
causes increased diameter of muscle fibre = hypertrophy
types of energy delivery (3)
immediate non oxidative oxidative during initial 2 mins, body relies on 'stored energy' and anaerobic glycolysis stores have to be re - filled at the end
immediate energy delivery
muscle cells have reserves of ATP and phosphocreatine
ADP + PCr (using creatine kinase) = ATP + creatine
as ADP accumulates: ADPs join together to form ATP and AMP using adenyl kinase
build up of ADP, AMP and Pi will stimulate metabolic pathways involved in energy productions
creatine = recycled into Phosphocreatine into mitochondria at rest
non oxidative energy delivery (anaerobic)
using glycolysis
muscle fibres store glycogen - 300-400g
substrates enter glycolysis ar 2 points
glycogenolysis of glycogen produces glucose-1-phosphate - converted into glucose-6-phsophate = enters glycolysis at reaction 2
- uptake of glucose from blood by GLUT4, glucose enter glycolysis pathway
pyruvate produced, pyruvate - converted to lactic acid/lactate
- process is very inefficient - 2 x ATP molecules per glucose
- H+ from lactic acid lowers cell pH = muscle fatigue
used at start of exercise/peak activity
advantage = produces ATP in absence of O2
disadvantage = ATP yield low and toxic products made
oxidative energy delivery (aerobic)
as tissue O2 delivery increases, energy production via oxid phos is stimulated
process is slower but more efficient = 30 molecules of ATP per glucose molecule
glucose sourced from blood, following breakdown of glycogen stored in liver
lactate converted back into pyruvate - feeds oxid phos
type IIx fibres release lactate into circulation - can enter other skeletal muscle cells or utilised by liver
extended periods of exercise
lactate and alanine used by liver to generate new glucose
during exercise - lactate cna be released from non exercising muscles, body acts to redistribute glycogen stores
mobilisation of non muscle lipids = increase in circulating fatty acids - taken by muscle
breakdown of triacylgylcerols stored in muscle
cells generate ATP through aerobic metabolism in mitochondria or via glycolysis (anaerobic) in cytoplasm
= 38 x ATP at ideal conditions
muscle fatigue
inability to maintain desired output, decline in force and velocity of muscle shortening
central fatigue
minor factor in trained exercise
brain is telling us to stop
types of peripheral fatigue (5)
high frequency low frequency ATP depletion lactic acid build up glycogen depletion
high frequency fatigue
altered Na/K cell balance, relevant more so to type II muscle fibres
low frequency fatigue
decreased release of calcium from sarcoplasmic reticulum = more apparent at low level stimulation - type I fibres
ATP depeletion
intense stimulation can cause large drops in ATP near sites of cross bridg formation and ATPases
lactic acid build up
high rates of lactate production leads to cellular acidification
Cardiac muscle
specific to heart
cardiomyocytes also striated like skeletal muscle
myocytes are shorter and more balanced, join together at intercalated disks
electrical coupling between adjacent myocytes at intercalated disk by gap junctions
action potential initiated in pacemaker cells of Sino-atrial node and propagates between cells via gap junctions
Smooth muscle
involved in mechanical control of organ systems e.g. digestive, urinary and reproductive system and control of blood vessels and airway diameter
control of smooth muscle more complex, cna involve circulating hormones, ANS input or inflammatory mediators e.g. histamine
2 classes of smooth muscle
multiunit - electrical isolation of cells allows finer motor control
unitary - gap junctions permit co-ordinated contraction
non striated, multiple actin fibres join at ‘dense bodies’ and thick filaments intersperse around thin filaments
large variations in action potential depending on muscle type, some cells can’t generate action potenitals but respond to graded changes in membrane potential - has impact on ion channels, allows Ca in or K out, can control muscle contraction
mechanisms for increasing intracellular calcium
- in skeletal muscle
excitation - contraction coupling
known as triad, at AI barrier
depolarisation activates L type Ca channels in the t tubule membrane = 2 effects
1 - leads to opening of L type Ca channels and influx of calcium into cell
2 - causes a mechanical tethering between L type Ca chanels in t tubule and Ca release channels (aka ryanodine receptors) in SR membrane = muscle contraction
Ca release channels in SR open and Ca moves into cytoplasm
mechanisms for increasing intracellular calcium
- in cardiac muscle
excitation - contraction
cardiac muscle does have t tubules but only close to on branch of SR = dyad
lie at Z line region
mo mechanical tethering between voltage gated Ca channels in t tubule to ryanodine receptors in SR
influx of Ca through t tubule channels activates ryanodine receptors = calcium induced calcium release
(CICR)
needs source of extracell calcium for contraction to occur
removal of calcium from cytoplasm:
terminates muscle contraction
1 - across cell mem by plasma mem calcium ATPase (PMCA) or electrogenic Na/Ca exchanger (NCX)
2 - back into SR via sarco-endoplasmic reticulum ATPase
mechanisms for increasing intracellular calcium
- smooth muscle
excitation - contraction
smooth muscle lacks t tubule and triad/dyad structures, instead shallow invaginations = caveolae
peripheral SR - encircles caveolae
central SR - runs through cell
change in mem potential = action potenital can activate L type Ca channels
leads to CICR via activvation of ryanodine receptors in SR membrane
activation of GPCR leads to IP3 production and sitmulation of IP3 receptors in SR membrane
sarcomere contraction
similar to skeletal and cardiac troponin couple: TnC = calcium binding complex TnT = interacts with tropomyosin TnI = inhibits actin binding sites
role of calcium and troponin in skeletal and cardiac muscle in cross bridge formation
inc Ca in cell means it binds to troponin complex = conformational change
moves tropomyosin and TnI = reveals actin binding sites
contraction continues whilst Ca levels are high
Ca drops = comes off complex and shifts tropomyosin back
covers actin binding site = contraction stops
contraction in smooth muscle
NO TROPONIN IN SMOOTH MUSCLE
2 other proteins - calponin and caldesman, tonically inhibit interaction of myosin and actin
Ca binds to calmodulin = myosin light chain kinase (MLCK) activated, which phosphorylates myosin head and activates it
activation of MLCK removes inhibtory effects of calponin and caldesmon facilitating cross bridge formation and contraction
to stop contraction - need to de-phosphorylate MLC which involves MLCP - myosin light chain phosphotase
