E-C coupling Flashcards
State the primary function of muscle
Generate force or movement in response to a physiological stimulus
What do muscles do in order to generate a mechanical response?
Transduce a chemical or electrical signal
What is the trigger for contraction of all 3 types of muscle?
An increase in Ca2+
What causes skeletal muscle to contract?
Contracts in response to neuromuscular synaptic transmission
A skeletal muscle fibre has a single NMJ where Ach receptors are located. What happens when ACh is released from the pre-synaptic nerve terminal?
It binds to nicotinic ACh receptors at the NMJ
Are nicotinic ACh receptors selective or non-selective?
What happens when ACh binds to them?
Non-selective cation channels
Open in response to ACh binding, resulting in depolarisation of Em known as end plate potential (epp)
What happens if the epp exceeds threshold for activating V-gated Na+ channels?
An action potential is generated
How is ACh rapidly inactivated?
Ach-esterase
How are skeletal muscles arranged?
Striated
Highly organised internal arrangement
What components make up a single skeletal muscle cell?
- Multiple nuclei
- Abundance of mitochondria
- 10-100 um in diameter and up to ~75cm in length
Define myofibrils
Specialised contractile elements that extend the entire length of the muscle fibre
What does thick and thin myofibril mean?
Thick- special assemblies of the protein myosin
Thin- made up primarily of the protein actin
Describe what an A band is made up of
What is the H zone?
Stacked set of thick filaments along with the portions of the thin filaments that overlap on both ends of the thick filaments
H-zone: The lighter area within the middle of the A band, where the thin filaments do not reach
What is the M-line and where is it located?
A system of supporting proteins that hold the thick filaments together vertically within each stack
Extends vertically down the middle of the A bnad within the centre of the H zone
What does the I band consist of and what is it visible in the middle of each I band?
The remaining portions of the thin filaments that dont project into the A band
Dense verticle line called the Z line
What is the area between two Z-lines called and what is it?
Sarcomere
Functional unit of the skeletal muscle
What are the characterisitics of the Z-line?
Flat, cytoskeletal disc that connects the thin filaments of the two adjoining sarcomeres
What is the width of a sarcomere?
2.5 um
List the levels of organisation in a skeletal muscle?
- Whole skeletal muscle (organ)
- Muscle fibre (single cell)
- Myofibril (specialised intracellular structure)
- Thick and thin filaments (cytoskeletal elements)
- Myosin and actin (protein molecules)
What do the thin filaments consist of?
Actin, tropomyosin and troponin
Explain the backbone of the thin filaments
A double stranded alpha helical polymer of filamentous-actin (F-actin molecules
What is F-actin associated with?
2 regulatory, actin proteins- tropomyosin and troponin
What does tropomyosin consist of?
2 identical a-helices that coil around eachother
head-to-tail contact between neighbouring tropomyosin molecules forms a ribbon that lies alongside the groove of the actin helix and physically covers the binding sites on actin molecules for attachment to what?
Myosin cross bridges
Prevents thin filaments attaching to cross bridges
Each heterotrimer of troponin interacts with a single molecule of tropomyosin, which inturn interacts directly with 7 actin monomers
What types of troponin are there?
Troponon T- binds to a single molecule of tropomyosin
Troponin C- binds Ca2+
Troponin I - binds to actin and inhibits contraction
What are thich filaments composed of?
Multiple myosin-II molecules
Each myosin-II molecule is a double trimer composed of what?
- 2x intertwined heavy chains
- 2x regulatory llight chains
- 2x alkali (or essential) light chains
What are the three regions of the 2 heavy chains?
A tail, hinge and a head region
What is the tail, hinge and head portion of the thick filaments?
Tail- a-helices that intertwine
Hinge- the molecule opens to form 2 globular heads
Head- (S1 fragments) are the cross bridges between the thick and thin filaments of the sarcomere
What do the heads of the heavy chains in thick filaments possess?
Binding site for actin and a site for binding and hydrolysing ATP
What do the head portions of each myosin form?
What do these components do?
Forms a complex with 2 light chains, 1 alkali and 1 regulatory
Alkali- stabilises the myosin head region
Regulatory- regulates the ATPase activity of myosin. The activity of this chain is regulated via phosphorylation by kinases
What happens to myosin-II heads in muscle contraction?
Where does the energy come from?
Bind to actin where the cross bridges become distorted and finally the myosin heads detach from actin
Hydrolysis of ATP
How does Ca2+ cause contraction?
Removes the inhibition of crossbridge cycling
Troponin contains troponin C that binds what?
Ca2+
What are the 5 steps of the cross-bridge cycle?
1) ATP binding
2) Atp hydrolysis
3) Cross bridge formation
4) Release of Pi from myosin
5) ADP release
What is the sliding filament mechanism?
Cross-bridge interaction between actin and myosin bringing about muscle contraction
What filaments on each side of the sarcomere slide inward over the stationary thick filaments?
What happens when they slide inwards?
Thin filaments
The thin filaments pull the Z-line (to which they are attached) closer together, so the sarcomeres shorten
Do the length of the filaments shorten during contraction and why?
No
Due to interactions of the filaments sliding over one another
What happens to the A, I band, H and Z zone during contraction?
A band- Determined by thick filaments so stays the same width
I band- Thin filaments not overlapping thick, so I band width decreases
H zone- Within A band, thick filaments not overlapping thin so width decreases
Z-line- Distance between decreases
What is rigor mortis and when does it occur?
“Stiffness of death”
3-4 hours after death and completes in ~12 hours
What happens during rigor mortis?
- Ca2+ rises after death
- The Ca2+ allows the regulatory proteins aside and lets actin bind the myosin cross bridges that are charged with ATP
- Dead cells cant produce more ATP so actin and myosin cannot detach
When does rigor mortis begin to reside?
The next several days after death as proteins involved start to degrade
What does E-C coupling stand for?
Excitation-contraction
What is the plasma membrane of a muscle cell also known as?
In skeletal muscle, what do they take the form of?
Sarcolemma
Transverse or T tubules
Where to T tubules penetrate the muscle- two points?
Junctions of the A and I bands
What is the muscle cell equivalant of the endoplasmic reticulum and what does it serve as storage for?
Sarcoplasmic reticulum
Ca2+
What is the combination of the T tubule membrane and its two neighhbouring cisternae called? What is the structures role?
Triad
Coupling of excitation to contraction in skeletal (and cardiac) muscle
What happens when the T tubule is depolarised?
Leads to Ca2+ release from the SR at the triad
What do the V-gated channels known as tetrads do?
Function as the voltage sensor in E-C coupling
Depolarisation evokes conformational changes in each of the four L-type Ca+ channels and has two effects. What are these effects?
Conformational changes allowing:
- Ca2+ to enter through the four channel pores
- Induce conformation change in each of the four subunits of Ca2+ channel located in the SR membrane
Where do Ca2+ channekls cluster?
In the portion of the SR that face the T tubules
What happens upon opening of the Ca2+ release channels in the SR?
Ca2+ stored in the SR enter the cytosol leading to a rapid increase in [Ca2+]i
What is CICR and what does it play a critical role in?
Local elevations in [Ca2+] can also activate the release channel in skeletal muscle
Plays a crucial role in E-C coupling in cardiac muscle
What does terminating contraction in all 3 muscle types require?
re-uptake of Ca2+ into the SR
What two ways can the cell extrude Ca2+?
- An Na-Ca exchanger (NCX)
- A Ca2+ pump at the PM (PMCA)
How is Ca2+ re-uptake mediated?
SERCA-type Ca2+ pump
Where is Calreticulin found in high concentrations? and what is it?
Within the SR of smooth muscle
Principal Ca2+ binding protein
What is the excitatory pulse used for?
If the contraction is to continue for longer periods, a series of calcium pulses must be initiated by a continous series of repetitve action potentials
Contractile activity far outlasts the electrical activity that initiated. What is the time delay called?
Latent period
When is the contraction process turned off?
When Ca2+ is returned to the SR when electrical activity stops
The thin filaments then return passively to their resting position
What part of the sarcomere does not change in length?
A band - dark band
Overlap between thick and thin filaments
