Lecture 11: Excitation-Contraction Coupling and the Cross-Bridge Cycle Flashcards
What is the name of the connective tissue that surrounds muscle fibres?
endomysium
What is the name of the connective tissue that surrounds that fasicle?
perimysium
What is the name of the connective tissue that surrounds the muscle?
epimysium
What is the purpose of the veins and capillaries surrounding the fasicles?
to supply the muscle fibres with O2 and nutrients
What is the purpose of the nerves that surround the muscle fibres?
to travel from the spinal cord to the muscle cells to innervate them
Where is Ca2+ stored in the muscle fibres?
in the sarcoplasmic reticulum
What is the purpose of the T-tubule?
to conduct the depolarisation into the muscle cell
What is the name of the skeletal muscle membrane?
sarcolemma
Where does the sarcoplasmic reticulum sit?
right next to the T-tubule
How does the AP that is conducted along the sarcolemma get inside the muscle cell?
via the T-tubule which propagates it inside the cell
What is the purpose of the mitochondria in the muscle fibre?
to generate ATP to be used for muscle contraction via the cross-bridge cycle
How does Ca2+ get into the SR?
it is actively pumped from the cytosol into the SR by a Ca2+ pump which requires ATP
How does the action potential get propagated along the sarcolemma?
via the opening of voltage gated ion channels which brings it into the muscle
What is the voltage sensor?
it is the dihydropyridine receptor which senses the action potential in the T-tubule and it relays it to the Ca2+ channel through physical coupling which opens the Ca2+ channel
What causes the Ca2+ channel to open?
when the voltage sensor senses the action potential and relays it to the channel through physical coupling
What is the name of the voltage sensor which opens the Ca2+ channel?
dyhydropyridine
What is the name of the Ca2+ channel?
ryanodine receptor
Which direction does Ca2+ flow when the ryanodine receptors open in the membrane of the SR?
out of the sarcoplasmic reticulum (into the cytosol)
What is the name of the Ca2+ pump which pumps Ca2+ back into the SR?
SERCA
What happens to the Ca2+ once it is in the cytosol?
it can interact with the actin
What happens if the Ca2+ stay high in the cytosol for too long?
the muscle contract for too long and there is continued force development
What is heat a biproduct of?
muscle activity (muscle contraction)
Why is heat a necessary biproduct?
because it maintains our body temperature
How is heat produced?
through processes which generate ATP and use ATP
Give an example of where heat is generated during a muscle contraction
when Ca2+ is pumped back into the SR via SERCA, SERCA hydrolyses ATP to ADP and phosphate to pump Ca2+ back into the sarcoplasmic reticulum and this generates heat. The production of new ATP also produces heat
What is is called when the body temperature increases above normal?
hyperthermia
What is it called when the body temperature decreases below normal?
hypothermia
What can hyperthermia cause? Why is this?
it can lead to nausea, vomiting, headaches, confusion and death because many processes stop working
What causes malignant hyperthermia?
mutations in ryanodine receptor or the dihydropyridine receptor (DHPR)
What is malignant hyperthermia?
an autosomal dominant, life-threatening disease
What triggers malignant hyperthermia?
volatile anaesthetics (ones that you inhale)
What happens during malignant hyperthermia?
The volatile anaesthetics interfere with the ryanodine receptor or the DHPR receptor with the mutations. These anaesthetics increase the function of these voltage sensors or Ca2+ channels causing a massive increase in the amount of Ca2+ released through the receptors. This excessive Ca2+ released from the SR store, there is muscle rigidity, spontaneous muscle contractions which leads to hyper-metabolic state because the Ca2+ has to be pumped back into the SR which uses ATP (which requires ATP production) which causes lots of heat
In the autoimmune disease myasthenia gravis, a rapid and prolonged sequence of action potentials at the NMJ will initiate progressively weaker muscle contraction BECAUSE more ACh is released from the motor neuron during each successive action potential
the first statement is true and the second one is false
Which is the thin filament, actin or myosin?
actin is the thin filament and myosin is the thick filament
What does a single action potential tigger?
a twitch
a short period of force generation which lasts just a short period of time
What two states can the myosin head be in?
flexed or energised (when it has ATP hydrolysed)
What is Mg2+ important for?
ATP hydrolysis
Describe the cross bridge cycling
the interaction between myosin and actin which generates force and allows these filaments to slide across each other
What does the thin actin filament have?
tropomyosin and troponin associated with them
What is tropomyosin?
This long thin beaded structure which runs across the entire length of actin which normally blocks the myosin binding sites
Where are the myosin binding sites?
on the actin
these are normally hidden by tropomyosin
What is troponin?
it is part of tropomyosin and it has a calcium binding site on it
troponin is the calcium sensor which senses calcium and causes a conformational change in tropomyosin to expose these myosin binding sites
Describe myosin
there are heavy chains and light chains and two heads
What are the two heads of myosin for?
both heads have both actin binding sites on the end of the head and ATP binding sites
Why can’t myosin bind to actin under resting conditions? ie. low sarcoplasmic Ca2+ (Ca2+ inside the muscle cell not the sarcoplasmic reticulum)
because tropomyosin is blocking the myosin binding sites
In order to get interaction between actin and myosin to generate skeletal muscle contraction, what needs to happen?
tropomyosin needs to be removed from the myosin binding sites
When Ca2+ is released from the sarcoplasmic reticulum into the inside of the muscle cell, what happens?
Ca2+ binds to troponin which causes a conformational change which causes tropomyosin to move off the myosin binding sites which allows the myosin head to bind and engage with actin. This is cross bridge formation
At the “end” of the cycle, where is ATP bound?
if ATP is available, it will bind the ATP binding sites on the myosin head
When ATP binds to the ATP binding site on the myosin head, what happens (at the “end of the cycle)?
the myosin head can disengage/come off the actin
What happens to the ATP when it is bound to the myosin head? What does this cause?
it is hydrolysed to ADP and phophate which energises the myosin head so it goes from a flexed position (relaxed) to an energised extended position
Where so the ADP and Pi go when the myosin head is energised?
they stay on the myosin head
If the myosin head is stimulated but there is no Ca2+ around, what happens?
the process stops here, there is no cross bridge formation because the myosin sites are blocked by tropomyosin
When the myosin head binds to actin, in order to generate force, what has to happen?
the ADP and Pi are released which flexes the myosin head and force is generated
To get repeating of the cycle after there has been force generated, what has to happen?
the myosin head needs to come off the actin so ATP binds
The cross bridge cycle requires ATP. What happens when there is no ATP around?
the myosin head stays attached to the actin and so the muscle stays stiff (rigor mortis after death)
