Skeletal Muscle Flashcards
Three main types of muscle and main function
1) Skeletal: attached to bones, responsible for movement
2) Cardiac: heart mass, contracts causing blood to pumped
3) Smooth: lines hollow organs, blood vessels, regulates their dimensions
Skeletal muscle
Voluntary
Striated
Long cylindrical cells
Multiple nuclei pushed to side
Cardiac Muscle
Involuntary
Striated
Connected via intercalated discs
Branched cells w/ 1-3 central nuclei
Smooth Muscle
Involuntary
NOT striated
Spindle shaped, one nucleus per cell
Lines internal organs
Motor unit
Motor neuron and all the muscle fibers it innervates
Skeletal muscle structure
Are attached to bone via tendons
Long (up to 35cm), Wide (0.1mm)
Cells are composed of fibrils (actin and myosin), containing contractile filaments
A-band
Both Actin and Myosin
I-band
Actin only
H zone
Myosin only
Filaments don’t overlap
Z-discs
Anchor thin filaments (actin)
Connect myofibrils to one another
T-tubules
Circle each sarcomere
At the end of each of the A bands and I bands meet
Allows AP to be carried deep within muscle cell
Extracellular fluid can go through T-tubule
Sarcoplasm reticulum (SR)
Calcium storage site
Terminal cisternae of SR lie close to T-tubule
Sarcolemma
Plasma membrane of muscle
Triad
T-tubule surrounded by terminal cisternae on either side
Titin
Anchors thick filament to Z-line
Thick filament
Myosin (globular head + tail)
Head is an ATPase (hydrolyses ATP)
that binds to actin
How is the myosin head arranged
Pointing away from M-line when stretched
Pointing in when relaxed
What Thin filaments structure, composed of
Double stranded helical actin chain
Troponin and tropomyosin are regulatory proteins
in skeletal and cardiac muscles
Tropomyosin
Thing strand
Can block myosin head from binding to actin
Troponin
Regularly arranged on tropomyosin
Calcium binding site
- changes shape when Ca2+ binds
Sliding filament theory
Thin filament pulled over thick filaments
Z-line pulled towards M-line
I band and H zone become narrower
4 major steps of Cross bridge cycle
1) Cross bridge formation
2) Power stroke
3) Detachment
4) Energisation of myosin head
Cross bridge formation
Myosin binds to actin binding site
Calcium binds to troponin, change shape, myosin-actin binding site exposed
Power Stroke
ADP released
Myosin head rotates
Importance of Calcium
Binds to troponin, the tropmyosin moves to expose the myosin binding sites on actin
Cross bridge cycle continues as long as calcium levels remain above threshold
Calcium regulation
Active Transport pumps move Ca2+ back into SR
Isotonic contraction of muscles
Shortening
SAME tension
Velocity variable
Isometric contraction of muscles
No shortening
Constant length
Different tension
Length-tension relationship
- what type of contraction does this occur?
- definition/theory
Isometric contraction- when muscle doesn’t shorten but tension increases
Maximum active force (tension developed) of sarcomere is dependent on degree of actin/myosin overlap determining the number of cross-bridges
@ optimal length what is actin and myosin like
Maximum number of cross-bridges formed
@ reduced size of zone overlap what is actin and myosin like
Fewer cross-bridges formed and reduced tension
@ zero zone of overlap what is actin and myosin like
Zero tension due to no interactions between myosin and actin
Active tension when less tension than normal
sarcomere lengths less than 2.0um filaments collide and interfere
What um is maximal force developed of muscle (normal working range of muscle)
2.0-2.2 um
Active tension when more tension than normal
Sarcomere length greater than2.2 active forces decline , less overlap, less cross bridges
Total tension equation
Sum of active tension and the passive tension
Passive tension
Resistance from CT around muscle cells resist stretch
More you stretch more the collagen and muscle prevents your from stretching
Total tension when stretching
The more you stretch, active force decreases, passive force decreases
Total can be more than 100%
Excitation-Contraction Coupling
AP enters T-tubules causing Ca2+ channels in SR to open
What happens when AP travels down motor neuron?
Axon terminal voltage gated channels open Ca2+ enters axon terminal
Vesicles containing Ach fuse with terminal membrane, releasing Ach into neuromuscular junction (synaptic cleft)
How are Ach receptors on activated on post-synaptic neuron?
Ach binds to ligand (Ach) gated channels causing them to open ;predominantly Na+, enters, K+ leaves muscle cell making it less negative (end plate potential) aka depolarisation of Post-SN
How is muscle AP triggered
Sufficient ligand channels are open and causes threshold to be reached
Voltage gated Na+ channels open and AP triggered
AP travels along sarcolemma into T-tubule
Excitation contraction coupling
- Ca2+ released
AP conducted down T-tubule causing coming into close contact with SR
Voltage-gated Ca2+ channels open in SR
Ca2+ released into cytosol/sarcoplasm
Ca2+ binds to
2 Ca2+ binds troponin, causing conformational change
When Ca2+ concentrations reach critical threshold myosin binding sites on actin exposed
When does muscle contraction end
Ends when Ca2+ levels fall
How is calcium levels reduced
Pumped back into SR by Ca2+ ATP-ase pumps
What is the result of actin on Ca2+ leaving
Troponin moves back covering myosin binding site
Creatine Phosphate
Can act as an ATP “store”
Creatine phosphate + ADP = creatine + ATP
Anaerobic
Anaerobic glycolysis properties
Good for short intense exercise: Fast but inefficient
Build up of lactate and H+ max. 120s
What does acidification of cell inhibit
phosphofructokinase (PFK)
Aerobic metabolism
Efficient, slower
Requires Oxygen, therefore good blood supply
Max 300W
What substances break down to form products of cellular respiration
Fatty acids, amino acids, pyruvic acid, oxygen from haemoglobin, myoglobin in muscle fibers
Myoglobin
High affinity for O2, and stores it
Two ways to increase muscle tension
Increase frequency of stimultion (e.g. AP’s)
Recruiting additional motor units
Temporal Summation
Additional AP’s initiated before Ca2- levels return to resting
Causes calcium levels to remain high and continuing force development
Tetanus
Muscle contraction sustained, by high frequency of AP’s
Type 1
Slow oxidative Moderate SR pumping capacity Small Diameter High mitochondria/myoglobin/blood supply Moderate glycolytic capacity Aerobic
Darker due to more mitochondria
Type 1 muscle fiber properties
Slow twitch
Units with neurons innervating slow aerobic cells
Maintain posture, walking, low intensity exercise
POSTRUAL
Type 2B
Fast twitch
Fast ATPase Rate- High SR pumping
Larger diameter, not relying on blood supply as much
Low mitochondria/myoglobin/blood supply
High glycolytic capacity
Anaerobic glycolysi
Glycolytic capacity
Measure of maximum capacity of glycolysis to generate ATP
which type of muscle fiber is recruited first
Type 1
Regulation of force dependent on
Number of AP’s coming down motor unit
The number of motor units recruited
Hypertrophy
Increase/growth in muscle size
Atrophy
Reduction in activity- loss of innervation
Relationship between motor unit and tension
As more units recruited, tension increases, as fast twitch fibres starting to be recruited
Atrial cells structure
100um long 10um wide
No t-tubules
Contract relatively weak
Allows co-ordinated contraction of all myocytes
How are atrial cells joined and what is the purpose of this?
Joined by gap junctions, allows electric activity to spread from one cell to next
Ventricular cells structure
100um long 30um wide
Branched
Have well developed T-tubular system which carries excitation into interior of cell
How are ventricular cells joined and what is the purpose of this?
By numerous gap junctions forming ‘sheets’ that wrap around ventricles
What is the purpose of desmosomes in relation to contraction
Prevent cells from separating during contraction
Intercalated disc function in relation to contraction
co-ordinated contraction of all myocytes
unlike skeletal muscle where fibres are recruited via motor neurons
Myogenic muscle
Initiates contractions without nervous input
How is AP generated in cardiac muscle
Sino-atrial node located in right atria
Where does this AP spread
Spreads throughout atria then Purkinje Fibres to the ventricles
How long is cardiac AP
- length relative to skeletal and nerve
> 100ms long
AP much longer than nerve and skeletal due to presence of ionic currents that hold the cell depolarised for a period comparable to that of a twitch
Why is there a plateau in tension development
Due to large Ca2+ current, slow to open slow to close, L-type channel, K+ moves out barely in little amounts
Can cardiac muscle tetani
No highly unlikely, due to absolute refractory period (long AP)
Three major stages in cardiac muscle AP
0- rapid depolarisation fast voltage gates Na+ channel
2- plateau due to slow voltage gated Ca2+ channel (L-type Ca2+ channel)
3- Repolarisation due to closing of Ca2+ and opening of K+ channels
Excitation coupling cardiac muscle
Depolarisation wave opens L-type Ca2+ channels in T-tubule
Ca2+ influx balanced by Na+/Ca2+ exchanger
What happens after Ca2+ enters Cytoplasm
Calcium induced calcium release
or RyRa
Ca2+ binds to RyRa opening channel allows Ca2+ to leave SR
What happens after Ca2+ released from RyRa
Ca2+ intracellular conc. allows Ca2+ to bind to troponin
What is special about troponin for cardiac muscle excitation?
Only ONE calcium specific site (skeletal muscle has TWO)
How is Ca2+ transported out of cell
Ca2+ ATPase into SR
sarcolemmal Na+/Ca2+ exchange
(3Na in, 1 Ca out)
mitochondria
sarcolemma Ca- ATPase
How is AP graded in skeletal muscle?
Recruiting more muscles
How is AP graded in cardiac muscle
Changing Ca2+ conc.
How is Heart rate (HR) set, and how is it modified
set by pacemaker in SAN
Rate modified by autonomic nerves releasing neurotransmitters
How is Stroke volume increased
Increased HR
Increased stretch of ventricles (length)
Certain neurotransmitters
Pacemaker potential
Slow depolarisation due to If channel ‘funny’ (mostly Na+ driven), SPONTANEOUSLY
Vagus nerve
Parasympathetic
Decreases heart rate
RELEASES ACh
What is special about ACh in innervation in cardiac muscle?
It is INHIBITORY, slows down HR
Sympathetic cardiac nerves
Can innervate both pacemakers, and ventricular myocytes
Affect heart rate AND stroke volume
Releases noradrenaline
How does ACh slow down heart rate
by hyperpolarising RMP, so takes longer to reach threshold
Decreases rate of spontaneous depolarisation
How does Noradrenaline increase heart rate
Increases rate of spontaneous depolarisation = increasing heart rate
“Automaticity”
Increasing HR increases… because…
Contractile force (Stroke volume)
Less time available for Ca2+ to be pumped out of cell = more Ca2+ in cell, increase CICR by SR = stronger contraction
Passive tension in heart
Lot of collagen, more stretch more total tension = more stroke volume
How Noradrenaline acts
INCREASES Ca2+ release
Increases frequency of discharge of SAN thus frequency of AP
binds to B receptors and via second messengers acts on
L-type channel (more Ca2+ entering cell)
Ca2+ ATPase in SR
so more Ca2+ ready to be released when next AP comes
Sympathetic Nervous System
Fight of flight response
Parasympathetic Nervous System
Rest and digest
Increase in Inotropy
Strengthening of muscle contraction
Basic structure of smooth muscle
Spindle shape
100-400um long 5um wide
Central nucleus
No sarcomeres Poor developed SR No troponin No t-tubules Few mitochondria No striation
Dense bodies
Act as z-lines to anchor actin to sarcolemma
Intermediate filaments attached
Single unit (visceral) smooth muscle
WAVE like contractions
Sheets of electrically coupled cells act in unison
e.g. hollow organs
Spontaneously active
Where is single-unit SM located
Blood vessels, hollow organs (digestive, respiratory, urinary, reproductive) RRUD
Multiunit SM
Independent cells contract to its own innervation
E.g. iris, vas deferens, piloerectors (hairs)
Why can smooth muscle contract further than skeletal and cardiac
Less organised, actin filaments don’t overlap as much and interfere
but slower
Initiation of contraction in smooth muscle
Due to voltage-gated Ca channels for cross bridge cycle
Increase in intracellular Ca, enter mostly through cell membrane channels
Contraction of smooth muscle can occur 3 three ways
Neural (iris)
Hormonal (uterus)
Spontaneous (gut) (myogenic)
What is the source of Ca in SM
Extracellular and SR via IP3
Ways which SM is regulated
Voltage, hormones, neurotransmitters, specific ions
How is Ca released from SR in SM
By ligand-gated second messenger pathways (IP3) and by RyR
What is activated when Ca2+ increase in SM
- what does it activate in turn
Calmodulin (binds 4 Ca2+ ions)
Activates myosin light chain kinase (MLCK)
which upregulates contraction
How is MLCK activated
regulation in SM is MYOSIN (not actin) based
Regulatory protein turned on by phosphate, then allowing myosin to hydrolyse ATP
When does contraction end in SM
when myosin light chain phosphatase (MLCP) removes phosphate group on myosin light chain
Why is SM contraction slower
Enzyme regulated (NOT calcium regulated)
Slow but efficient
What favours relaxation in SM
Increased MLCP
Decrease intracellular Ca2+
What favours contraction in SM
Increased MLCK activity (Ca2+ regulated)
How can SM contraction be graded
Difference in modulation of MLCK and MLCP
What can modulate SM contraction
Stretch Neurotransmitters Hormones Environment Histamine Adenosine Prostacyclin Nitric oxide (NO)
Nitric Oxide (NO) function in modulating
Inhibits cGMP-dependent mechanism which contract proteins
What innervates SM what do they do
Autonomic nerve fibres branch, “diffuse junction”
What are the subunits of Autonomic nerve fibres and what do they contain
Varcosities (in terminal axon) release neurotransmitters into synaptic cleft
What happens when you stretch smooth muscle
Initially contract, effectively resisting the stretch
(e. g. blood vessels trying to maintain blood flow constant)
- Stretch activated calcium channels
Over time slowly relaxes, adapting to change in length (e.g. gut)
- via Ca dependent K+ channels, hyperpolarising membrane potential
Stress relaxation
Your constant deformation (e.g. stomach) can be steady but your stress relaxation can decrease therefore you can eat more
