Muscle Physiology Flashcards
1
Q
what are muscle tissues derived from?
A
mesoderm
2
Q
what are the progenitor cells for muscle?
A
myoblasts -> myotubes
3
Q
what are satellite cells?
A
stem cells that reside on muscle fibres and become activated upon injury to differentiate to generate new muscle fibres and repair skeletal muscle tissue
4
Q
what happens to satellite cells when muscle is injured?
A
move to site of injury, proliferate and undergo differentiation?
5
Q
what is muscle degeneration?
A
an inflammatory response - formation of fibrosis, scar tissue develops
6
Q
which muscle fibres have satellite cells?
A
skeletal
7
Q
how can cardiac muscle undergo limited repair?
A
stem cells circulating in blood
8
Q
how many skeletal muscles are there in human body?
A
around 600
9
Q
what is epimysium?
A
sheath of connective tissue enveloping whole muscle, connecting to tendons
10
Q
what is the first subdivision of muscle?
A
fascicles
11
Q
what are fascicles surrounded by?
A
perimysium
12
Q
what are muscle fibres surrounded by?
A
endomysium/basal lamina
13
Q
what are myofibrils made of?
A
end-to-end chains of sarcomeres
14
Q
what are the contractile units of muscle?
A
sarcomeres
15
Q
what is the basis of the term striated muscle?
A
characteristic banding from sarcomeres
16
Q
why are the A bands of sarcomeres dark?
A
anisotropic and contain thick filaments
17
Q
why are the I bands of sarcomeres light?
A
isotropic, contain thin filaments
18
Q
where are Z lines?
A
in centre of I bands, either end of sarcomeres
19
Q
where is the M line?
A
centre of A bands, centre of sarcomere
20
Q
what happens to the respective width of the A and I bands in sarcomeres when muscle contracts?
A
I bands get thinner, A band stays same width
21
Q
what are the 3 cytoskeletal filaments?
A
actin, microtubules, intermediate filaments
22
Q
which are the thickest most rigid cytoskeletal filaments?
A
microtubules
23
Q
what are the key functions of microtubules?
A
acting as tracks for intracellular trafficking, forming mitotic spindle that separates chromosomes during cell division
24
Q
what are the functions of intermediate filaments?
A
important roles in cell mechanics, maintaining cell structural integrity
25
what are the functions of actin?
key structural polymer, actin networks support cell shape, drive cell deformations in most animal cells.
26
what is the structure of actin monomers?
assemble head to tail to form double helix so actin filament has 2 structurally distinct ends- a plus and a minus
27
where does active polymerisation occur in non muscle cell actin filaments?
at plus ends
28
where does depolarisation occur in non muscle cell actin filaments?
at minus ends
29
where are the plus ends of actin filaments anchored?
at Z-disk
30
what are the 3 classes of cytoskeletal motors?
myosin, dyneins, kinesins
31
what are cytoskeletal motors?
proteins which convert chemical energy of ATP into mechanical energy
32
which cytoskeletal motors are microtubule based?
dyneins and kinesins
33
what is the function of dyneins?
orchestrate transport of cargoes along the axon
34
what is the function of kinesins?
orchestrate transport of cargoes along axon
35
how many human myosins are there?
39
36
how many classes of human myosins are there?
12
37
what is the function of myosin 6?
cargo transport
38
what is the function of myosin 1?
attachment of actin to plasma membrane
39
what is the function of myosin 2?
largest myosin molecules, generate contractility by cross linking and pulling actin filaments
40
what is the structure of myosin?
a hexamer, 2 heavy chains, 2 essential light chains, 2 regulatory light chains
41
what does each myosin heavy chain contain?
actin-binding site, flexible hinge region and long tail region
42
what are both the heavy and light chains of myosin regulated by?
phosphorylation
43
what is tropomyosin?
rod-shaped molecule that forms alpha-helical subunits that become packed into depth of groove that is formed by the actin chains of an actin filament
44
how many actin units does 1 tropomyosin molecule span?
7
45
what does tropomyosin do in resting skeletal muscle?
prevents binding of actin to myosin
46
what is the function of troponin?
moves tropomyosin deeper into the groove to to uncover the myosin binding site on actin
47
what is alpha-actinin?
rod-shaped homodimer of about 35nm in length with an actin binding site on each end
48
what is the function of alpha-actinin?
cross-link actin filaments at the z-disks
49
what are nebulin and titin?
large structural proteins anchored at the Z-disk which contribute to the structural integrity of the sarcomere
50
what is the role of titin?
stabilises myosin thick filaments in the middle of the sarcomere preventing them from deviating too much from the central position
51
what is the diameter of cardiac muscle cells?
up to 10 microns
52
what is the length of cardiac muscle cells?
up to 200 microns in length
53
which are larger, cardiac or skeletal muscle fibres?
skeletal muscle fibres
54
how are adjacent cardiac cells coupled to each other?
mechanically and electrically in a branched and an end-to-end manner by intercalated disks resulting in a syncytium
55
what do smooth muscle cells line?
the walls of hollow organs (gut, airways, blood vessels, urogenital system)
56
what is the load against which smooth muscle works?
the pressure within the tubular structures it lines
57
how is pressure maintained in organs such as blood vessels?
by tonic contraction of smooth muscle
58
how are contents propelled through tubes such as the gut by smooth muscle?
phasic contraction used to propel the contents through the tube
59
what is smooth muscle better suited to than skeletal muscle?
sustained contractions
60
which contracts/relaxes more slowly, smooth or skeletal muscle?
smooth muscle
61
what are the properties of smooth muscle cells?
elongated, often spindle-shaped, much smaller than skeletal muscle fibres
62
how large are smooth muscle cells?
3-5um diameter, up to a few hundred um long
63
why are smooth muscle cells 'smooth'?
they have no visible striations or sarcomeres in their cytoplasm
64
how are the actin and myosin filaments of smooth muscle cells arranged?
thick myosin and thin actin filaments oriented along length of cell
65
what are the contractile bundles in smooth muscle cells attached to?
dense bodies in the cytoplasm
66
how are dense bodies in the cytoplasm of smooth muscle cells connected to each other?
through intermediate filaments
67
what are dense bodies connected to in the membrane of smooth muscle cells?
attached to adhesion plaques
68
what are dense bodies in smooth cells analogous to in skeletal muscle cells?
Z disks and alpha-actinin
69
what is the function of dense bodies?
act as anchors for filaments to allow efficient shortening of the cell
70
how are most smooth muscle cells connected?
extensive electrically-conducting gap junctions between cells which allows propagation of waves of electrical excitation/intracellular messengers through the tissue
71
what happens in the cross-bridge cycle?
myosin head without bound nucleotide tightly attached to actin filament, ATP binding leads to conformational changes, reduces affinity of myosin for actin, myosin head releases actin filament, myosin head remains very close to actin filament ready to bind again. ATP binding also causes myosin head and neck to pivot into cocked position causing myosin head to move along actin filament. ATP is hydrolysed, ADP and Pi stay bound to myosin. cocked myosin binds actin filament weakly, triggering Pi release, in turn affinity for actin increases. Pi release triggers 'power stroke', myosin returns to original conformation, actin filament pulled toward centre of sarcomere, triggers ADP release, return to original state
72
what causes rigor mortis?
when a person dies all ATP rapidly depleted, any myosin attached to actin filament will remain attached until proteins decay
73
how many ATP molecules are consumed in each cross-bridge cycle for 1 step of a myosin along 1 actin filament?
1
74
how many myosins does each sarcomere filament have?
around 300
75
how many sarcomeres can large muscles like biceps contain?
100,000
76
what is the ATP in a cell enough for?
around 8 twitches
77
what does creatinine phosphate do?
provides intracellular backup system that can provide enough ATP for around 100 twitches
78
what are used to produce ATP at increased exercise activity?
aerobic and anaerobic mechanisms that mostly use glucose as a substrate
79
what is the role of calcium in skeletal and cardiac muscle contractility?
regulates binding of myosin to actin via tropomyosin and troponin
80
what are the 3 subunits of skeletal muscle?
TnI (inhibitory), TnC (calcium ions), TnT (tropomyosin)
81
what happens to skeletal muscle troponin when intracellular calcium increases?
TnC binds up to 4 calcium ions, leads to conformational change which causes TnI to release its hold on actin, tropomyosin displaced deeper in actin double helix groove so myosin-binding sites become accessible
82
what is the difference between activation of contraction by calcium in cardiac vs skeletal muscle?
cardiac TnC binds 3 calcium ions not 4
83
what is the main activation mechanism of smooth muscle contraction?
every myosin molecule has 2 regulatory light chains (Myosin Regulatory Light Chains) regulated by phosphorylation, leads to activation of myosin activity through conformational change enhancing actin binding and increase in ATPase activity
84
how is MRLC phosphorylation controlled in smooth muscle?
intracellular calcium through regulatory protein calmodulin
85
what is calmodulin closely related to?
TnC (calcium binding subunit of troponin)
86
what happens when calmodulin binds calcium?
Ca-CaM complex activates kinase MLK, phosphorylates MRLCs
87
how long can maximal contraction take to occur in smooth muscle?
up to 1s
88
how much slower is ATP hydrolysis in the cross-bridge cycle than in skeletal myosins?
10x slower
89
what does intracellular calcium decrease lead to in skeletal and cardiac muscle?
termination of contraction
90
what is needed for termination of contraction in smooth muscle?
intracellular calcium decrease AND MRLC dephosphorylation
91
what mediates MRLC dephosphorylation?
myosin light chain phosphatase (MLCP)
92
what does experimental evidence suggest happens in MRLC dephosphorylation occurs when myosin is bound to the actin filament?
myosin remains bound with a high affinity - cross-bridges in this state are latch bridges
93
what do latch bridges allow?
maintenance of tension without cross-bridge cycling or ATP consumption
94
why is smooth muscle up to 300x more efficient than skeletal during maintained contractions?
latch bridges formed by MRLC dephosphorylation while myosin is bound to actin
95
what proteins regulate contraction at the actin filament level in smooth muscle?
caldesmon and calponin
96
what do caldesmon and calponin do?
bind actin and smooth muscle tropomyosin and inhibit interaction between actin and myosin
97
what binds caldesmon and calponin and what does this do?
Ca-CaM complex, relieves their inhibitory effects on actin-myosin binding
98
what are muscle dystrophies?
inherited conditions resulting in disorganisation of the myofilaments and eventual paralysis
99
what proteins are some muscle dystrophies associated with?
titin and dystrophin
100
what does dystrophin do?
connects the actin thin filaments to the extracellular matrix
101
what is the extracellular matrix in muscle fibres?
network of elastic filaments that surrounds the muscle fibres
102
what is Duchenne muscular dystrophy?
a rare genetic X-linked recessive condition which results from mutations disrupting dystrophin
103
what happens to muscles in the absence of dystrophin?
they are easily damaged damage accumulates resulting in general muscle weakening over time
104
what are hypertrophic cardiomyopathies?
an inherited condition characterised by thickening of ventricular walls and a smaller ventricular chamber
105
what are many HCMs caused by?
a single mutation in cardiac beta myosin heavy chain
106
what is a motor unit?
set of all muscle fibres innervated by 1 presynaptic neuron
107
what is tone?
low level of activity shown by small motor units at rest
108
what produces muscle tone?
stretch reflex from muscle spindle receptors
109
what is tone responsible for at rest?
firmness of muscles
110
what is poliomyelitis?
a disease which destroys motor axons
111
where is acetylcholinesterase found?
in membrane in synaptic cleft
112
what is the structure of NAChRs?
pentameric molecule, central cation channel, ligand-gated. 2 binding sites for ACh
113
how many ACh binding sites do NAChRs have?
2, both must be bound for cation channel to open
114
when does the NAChR become desensitised?
if ACh levels high for a long time
115
what is the NAChR channel permeable to?
sodium and potassium ions and calcium a little bit
116
when does the graph cross the x-axis if plot inward flux of positive current and outward flux of positive current against membrane potential in postsynaptic membrane?
near 0
117
what is seen in EPPs in curare-treated muscle when they are too small to trigger action potentials?
peak size of EPPs decays exponentially with distance from endplate because more endplate current leaks to outside across muscle fibre membrane
118
what is the difference in selectivity of the 4 calcium binding sites in skeletal muscle?
2 are more selective for Ca2+ than Mg2+
119
what does a muscle AP trigger from the sarcoplasmic reticulum?
Ca2+ release
120
why is the transverse (T) tubular system required?
to carry surface excitation deep into skeletal muscle fibre to allow uniform, rapid Ca2+ release across entire cross-section of each fibre
121
what is the T tubular system?
invaginations of membrane which penetrate into interior of muscle fibre, lumen continuous with extracellular space
122
what increase in SA does the T tubular system cause?
6-10 times greater
123
what is each individual myofibril in skeletal muscle surrounded by?
a T tubule
124
where do T-system networks occur in the sarcomere in mammalian skeletal muscle?
at junctions between A and I bands
125
where do T-system networks occur in the sarcomere in mammalian cardiac and frog skeletal muscle?
at the Z line
126
when can local surface depolarisation of muscle fibre using a fine micropipette produce contraction of underlying sarcomeres?
if micropipette located precisely on external opening of T-tubules
127
what system does the SR form?
longitudinal system of tubules and sacs which come into close contact with T-tubules at terminal cisternae
128
where does the SR come into close contact with T-tubules?
at terminal cisternae
129
what is the arrangement of cisternae and T-tubules?
triad arrangement- 2 terminal cisternae sandwiching transverse tubule to give rise to triad arrangement
130
how do muscle APs propagate into T-tubular system?
as along a nerve- allowing efficient, rapid propagation of excitation into fibre
131
how do VGNaCs amplify depolarisation of the T-system membrane?
conduction of Na+ ions from T-system into fibre
132
how do VGKCs repolarise the T-system membrane?
by conducting K+ from fibre into T-system
133
how is the magnitude of the equilibrium potential for K+ across the T-system membrane reduced over the course of a few APs?
T-system volume less than 0.5% of the whole cell volume so K+ can build up in T system, reduces magnitude of equilibrium potential
134
why is the T-system more permeable to Cl- than K+ at rest?
due to Clc1 chloride channels
135
why does Cl- tend to keep membrane potential of the T-system well-polarised at rest?
Cl- is passively distributed so equilibrium potential of Cl- is similar to resting membrane potential
136
what are DHPRs?
voltage sensors (L-type calcium channels) in membrane of T-tubules
137
what are DHPRs mechanically linked to?
calcium release channels called ryanodine receptors in SR of skeletal muscle
138
what does depolarisation of T-tubular membrane cause in DHPRs?
conformational change , causes conformational change in sarcoplasmic reticulum ryanodine receptor calcium channels which causes them to open
139
how is calcium concentrated in the sarcoplasmic reticulum?
by ATP-consuming calcium pumps (SERCA pumps)
140
what is the function of calsequestrin?
binds Ca2+ in the SR, reduces the gradient against which SERCA pumps have to work
141
what does opening of ryanodine receptors allow?
Ca2+ to flow out of SR down electrochemical gradient to raise conc. within muscle fibre cytoplasm, Ca2+ binds to TnC initiating contraction
142
how are calcium levels in the sarcoplasm reduced leading to relaxation of muscle?
calcium is resequestered in sarcoplasmic reticulum by calcium pumps
143
what is force exerted by a muscle more commonly referred to?
tension
144
what is the amount of work done a product of?
force and distance
145
what is power?
the rate of doing work
146
what direction do crossbridges on each half of a filament work in?
parallel
147
what is the tension developed by a thick filament the sum of?
the tension developed by its individual crossbridges at 1 end
148
how do length changes in series combine?
add together
149
why is the tension developed in each myofibril the same as in each single sarcomere in the chain?
the sarcomeres are in series
150
what is the maximal force developed by a whole muscle proportional to?
the total number of thick filaments in a cross-section
151
what is the effect of lengthening a muscle by adding more sarcomeres in series?
increases the total distance of shortening proportionally
152
what is the force of 1 myofibril?
number of thick filaments per sarcomere x force of 1 thick filament
153
what is the total muscle force?
number of thick filaments x force of 1 thick filament x myofibrils in whole muscle
154
what is total muscle length change?
sarcomeres per myofibrils x length change of 1 sarcomere
155
what is the effect of making muscle fatter?
increases muscle force
156
what is the effect of making muscle longer?
increases muscle contraction velocity
157
what is isometric contraction?
contraction of a muscle at constant length
158
what is isomeric tension the sum of?
passive tension due to elasticity of connective tissue and cytoskeleton in muscle; active tension due to operation of contractile apparatus
159
what is isotonic contraction?
contraction of a muscle under constant load
160
how is isometric tension measured?
isometric contraction at different lengths of muscle
161
what does the isometric length-tension relationship of a muscle show?
maximal tension developed over a narrow range of lengths corresponding to physiological working range
162
how is active tension calculated?
total tension - passive tension
163
when is maximal force developed in a sarcomere?
when all crossbridges engaged on thin filament, but opposing thin filaments don't overlap
164
what reduces crossbridge efficiency in a single sarcomere?
collision of thin filaments as sarcomere shortens, then thick filaments colliding with Z discs
165
what is isotonic contraction?
contraction of muscle at constant tension
166
what is the relationship between velocity and load in muscle contraction?
inverse
167
what is a twitch?
the whole mechanical response to a single action potential
168
what is tetanus?
sustained contraction
169
what produces tetanus?
frequency of action potentials above a certain value producing a constant maximal occupation of TnC by calcium
170
what is the arrangement of myofibrils in a straight strap muscle?
aligned parallel to axis of contraction of whole muscle
171
what is the arrangement of myofibrils in pennate and triangular muscle?
myofibrils at an angle to axis of bone- can increase total force generating capacity by allowing for more muscle fibre to be attached to the bone
172
what is the parallel elastic element of muscle?
elasticity of the relaxed muscle due to membranes and other connective tissue in parallel with myofibrils
173
what is the series elastic element of muscle?
springiness of material in series with sarcomeres (tendons, terminal connective tissue, z disks) and elasticity of crossbridges and filaments
174
diameter of slow oxidative muscle?
small
175
force/area of slow oxidative muscle?
low
176
Vmax of slow oxidative muscle?
low
177
myosin heavy chain in slow oxidative muscle?
MHC-1
178
diameter of fast oxidative muscle?
medium
179
what is type 1 muscle?
slow oxidative
180
what is type 2a muscle?
fast oxidative
181
what is type 2b muscle?
fast glycolytic
182
force/area of fast oxidative muscle?
medium
183
Vmax of fast oxidative muscle?
medium
184
myosin heavy chain of fast oxidative muscle?
MHC-2a
185
diameter of fast glycolytic muscle?
large
186
force/area of fast glycolytic muscle?
high
187
Vmax of fast glycolytic muscle?
high
188
myosin heavy chain in fast glycolytic muscle?
MHC-2b
189
fatigue resistance of slow oxidative muscle?
high
190
fatigue resistance of fast oxidative muscle?
medium
191
fatigue resistance of fast glycolytic muscle?
low
192
mitochondria in slow oxidative muscle?
a lot
193
mitochondria in fast oxidative muscle?
a lot
194
mitochondria in fast glycolytic muscle?
few
195
oxidative capacity of oxidative muscle (fast and slow)?
high
196
oxidative capacity of fast glycolytic muscle?
low
197
glycolytic enzymes in slow oxidative muscle?
low
198
glycolytic enzymes in fast oxidative muscle
medium
199
example of fast glycolytic muscle?
chicken breast gastrocnemius
200
example of fast oxidative muscle?
pigeon breast
201
example of slow oxidative muscle?
human soleus
202
glycolytic enzymes in fast glycolytic muscle?
high
203
how does electrical signal propagate from 1 cardiac cell to another?
through gap junctions
204
where is the cardiac activity that controls heart contractions initiated?
in the heart independently of nervous system
205
how is cardiac action potential initiated in the normal heart?
in sinoatrial node by specialised cardiac myocytes with pacemaker activity
206
what is the primary function of cardiac myocytes in the SAN?
generation and conduction of pacemaker potential
207
what is the difference between myocytes in the SAN and atrial/ventricular myocytes?
SAN myocytes have fewer myofibres and mitochondria and smaller SR
208
how many times/min does the SA node fire?
60-80
209
what is the electrical connection between atria and ventricles?
atrioventricular node
210
what electrically isolates the atria and ventricles from each other except for at the AVN?
a fibrous AV ring
211
what creates delay in contraction spreading to the ventricles?
conduction through AV node is slower than surrounding muscle tissue
212
where does the electrical signal propagate from the AC node?
Bundle of His and Purkinje fibres- specialised myocardial cells that act as conducting tissue
213
what is the main function of the bundle of His and Purkinje fibres?
conducting electrical signal rather than contraction
214
where does electrical signal propagate from Purkinje fibres?
fibres split into 2 branches, propagates into the 2 ventricles
215
what ensures ventricles contract from apex to base?
fibre arrangement and speed of signal propagation
216
what is phase 0 of an AP in cardiac myocytes?
rapid depolarisation phase
217
what is phase 1 of an AP in cardiac myocytes?
initial brief rapid depolarisation
218
what is phase 2 of an AP in cardiac myocytes?
plateau
219
what is phase 3 of an AP in cardiac myocytes?
terminal repolarisation restores membrane potential to resting level
220
what is phase 4 of an AP in cardiac myocytes?
electrical diastole- heart waiting for another electrical trigger to restart the cycle
221
what causes the rapid depolarisation in phase 0 of ventricular muscle cells?
voltage gated Na+ channels activated, slower opening of Ca2+ channels
222
what causes the initial rapid repolarisation in phase 1 of ventricular muscle cells?
Na+ channels close into inactive state, K+ channels open
223
what causes the plateau in 2 of ventricular muscle cells?
Ca2+ channels not inactivated, remain open, Ca2+ influx more or less balances K+ efflux. Ca2+ channels are L-type voltage gated DHPRs, sensitive to calcium blockers which inhibit plateau calcium current
224
what causes the terminal repolarisation in phase 3 of ventricular muscle cells?
delayed activation of K+ channels leading to repolarisation
225
what causes the electrical diastole in phase 4 of ventricular muscle cells?
membrane returns to resting potential
226
why do cardiac myocytes have long refractory period?
AP remains high through plateau phase so Na+ channels stay inactive through that phase- ensures summation and tetanus don't occur
227
what is the most important feature of APs in SAN cells?
SAN cells don't have true RP as membrane potential always changing so don't depolarise as much as other cells
228
what is the current due to in SAN cell APs?
non-specific cation channel (HCN channel) which has mixed permeability for both Na+ and K+
229
why is the current in SAN APs called the 'funny' current?
HCN channel has unusual property of opening upon hyperpolarisation
230
when do HCN channels open in SAN APs?
at end of phase 3 depolarisation, leads to inward cation current driving slow membrane depolarisation in phase 4
231
how can most intrinsic mechanisms that regulate heart function be modulated?
autonomic impulses from sympathetic and parasympathetic nervous systems, indirectly through circulating levels of epinephrine released into blood
232
how does vagal stimulation through ACh slow heart rate?
increase in membrane potassium conductance which hyperpolarises membrane of SA by decreasing If, which decreases slope of Phase 4 depolarisation
233
how do sympathetic transmitters norepinephrine and epinephrine increase heart rate?
increase If and reduce phase 3 repolarisation, results in increased heart rate. leads to higher but shorter plateau in ventricular cells- stronger contraction
234
how does the T-tubule system work in cardiac myocytes?
Ca2+ released through Calcium Induced Calcium Release- Ryanodine receptors activated by extracellular Ca2+ that enters through DHPRs rather than mechanical coupling with DHPRs
235
what are the consequences of calcium induced calcium release?
risk of Ca2+ overload, so needs sarcolemmal Na+/Ca2+ exchanger. Ca2+ also re-sequestered in SR between APs. Ca2+ controlled by SERCA pump inhibited by Phospholamban (PLN). amount of extracellular Ca2+ influences how much Ca2+ released from SR
236
what mediates PLN phosphorylation to stop its inhibition of SERCA?
PKA as a result of epinephrine signalling
