1
Q
What is the average range of an animal cell?
A
Animal cells are around 10-30 micrometres
2
Q
What are the primary components of a eukaryotic cell?
A
- Nucleus
- Membrane-bound organelles
- Lysosomes and peroxisomes
- Microtubules
- ER
- Mitochondria
- Cytoskeleton
- Ribosomes
- Vesicles
- Golgi apparatus
- Chloroplasts
- Nuclear Membrane
- Plasma membrane
- Cell wall
- Vacuoles
3
Q
What is the major difference between prokaryotic and eukaryotics cells?
A
Eukaryotics cells have membrane-bound organelles
4
Q
What is the purpose of biological membranes (in general)
A
A living system must be separated from its environment if it is to maintain complex order – in the cell this is done by biological membranes
5
Q
What are the two types of biological membranes found around cells?
A
- Cell membrane
- Plasma membrane
6
Q
List two key properties that all biological membranes must have
A
- Selective permeability
- Signal transduction
7
Q
List the four primary functions of biomembranes
A
- Barrier between the cell and its environment
- Serve as boundaries of organelles
- Impermeable to macromolecules and charged molecules (i.e. selective permeability)
- Platform for communication between the cell and its environment (i.e. signal transduction)
8
Q
Explain how the phosphlipid bilayer can form
A
Phospholipids have hydrophilic (polar) heads and hydrophobic (non-polar) tails therefore self organise into a bilayer (with the heads on the outside and the tails on the inside)
This self-organisation can also form micelles
9
Q
What are the two major functions of the lipid bilayer?
A
- The hydrophobic core acts as an impermeable barrier preventing the diffusion of water-soluble (hydrophilic) solutes across the membrane.
- The bilayer maintains cellular architecture (due to van der Waals interactions)
10
Q
Outline the structure of phosphatidylcholine
A
- Hydrophobic tail (fatty acid) composed of two fatty acyl chains esterified to the two hydroxyl groups in glycerol phosphate
- Hydrophilic head (choline + phosphate + glycerol) attached to phosphate group
11
Q
How does the presence of the following fats affect membrane composition?
- Cholesterol
- Short-chain fatty acids
- Unsaturated fats
A
- Cholesterol = causes ordered structure (found in abundance in the PM)
- Short-chain fatty acids = increases membrane fluidity
- Unstaurated fats = increases membrane fluidity
12
Q
What is the fluid mosaic model
A
The cell membrane consists of lipids interspersed with integrated proteins - this is the fluid mosaic model
13
Q
List and describe the three ways in which proteins can interact with the membrane
A
Integral Membrane Proteins
- Permenantly attached to the membrane
- Classified according to their relationship with the bilayer
Peripheral Membrane Proteins
- Temporarily attached to the membrane (either directly to the bilayer or via an integral membrane protein)
Lipid-Anchored Membrane Proteins
- Protein covalently bonded to the membrane via a fatty acid
14
Q
List the major functions of membrane proteins
A
- Membrane receptor proteins relay signals between the cell’s internal and external environments.
- Transport proteins move molecules and ions across the membrane.
- Membrane enzymes may have many activities
- Cell adhesion molecules allow cells to identify each other and interact
15
Q
List the molecules that the membrane (PM) is (a) permeable to and (b) impermeable to
A
- Permeable -* water + small uncharged molecules (eg: oxygen)
- Impermeable* - macromolecules + charged ions + hydrophilic molecules
16
Q
How to molecules to which the membrane is impermeable to enter the cell?
A
Via pores or channels
17
Q
What are the two types of coupled transporters?
A
- Symporters - sugars and amino acids can be dragged into the cell with Na+, as it moves down its concentration gradient
- Antiporters - other molecules can move in the opposite direction to Na+ (e.g. H+; Na+-H+ exchanger for intracellular pH regulation)
18
Q
What are the relative concentrations of the main ions (intra- and extracellularly)?
A
Extracellular Concentrations
- Sodium = HIGH
- Chloride = HIGH
- Potassium = LOW
Intracellular Concentrations
- Sodium = LOW
- Chloride = LOW
- Potassium = HIGH
19
Q
How does the Na/K ATPase pump work?
A
Exchanges 3 sodium ions from inside the cell for 2 potassium ions outside the cell
- Transport of 2K+ from left (extracellular) to right (intracellular) in exchange for 3Na+. It is “electrogenic”, i.e. creates a negative intracellular potential.
- Mediated by successive conformational transitions of the pump molecule
- Driven by phosphorylation of an aspartyl residue using ATP
- Followed by hydrolysis of the aspartylphosphate.
20
Q
What are the two consequences of the Na/K ATPase?
A
- Ionic gradients are created
- Less Na+ and more K+ inside the cell than outside.
- A charge gradient is created
- As more positive charges are pushed out than are coming in. This results in the inside of the cell being at a more negative potential than the outside.
21
Q
What is membrane potential?
(i.e. how does it arise?)
A
Membrane potential arises due to a difference in electric charge on the two sides of a membrane.
22
Q
What is resting membrane potential
A
-70 mV
23
Q
How does glucose enter the cell
A
- The cell membrane is impermeable to glucose
- Glucose enters the cell via glucose transporters
- Transport of glucose is via facilitated diffusion
- Glucose transport is via symporters
- Glucose transport is coupled to sodium
24
Q
What are epithelial cells?
A
Epithelial cells - cells forming continuous layers, these layers line surfaces and separate tissue compartments
25
Where are epithelial cells normally found?
* Lining organs (eg: stomach, SI, kiney etc.)
* Found within ducts and glands
* Forming the structure of the lungs and alveoli
* Act as sensory receptors
* First cell types of the embryo
26
List the functions of epithelial cells
* Boundary & Protection – cover the inner and outer linings of the body cavities and act as a barrier to pathogens and other harmful foreign substance
* Sensory – they are avascular however they are innervated
* Transportation – epithelia in the intestinal lining aid in transportation
* Absorption – certain epithelia are capable of contributing to active transport mechanisms
* Secretion – specialised epithelial cells (eg: goblet cells) secrete fluids
* Movement – some epithelial cells are ciliated which enable the movement of substances (eg: mucous)
27
What major components form the ECM?
Generally composed of **fibrillar (or reticular) proteins** (e.g. collagens, elastin) embedded in a **hydrated gel** (proteoglycans or “ground substance”) (i.e. non-fibrillar component)
28
List the major functions of the ECM
* Provides physical support
* Determines the mechanical and physicochemcial properties of the tissue
* Influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts
* Essential for development, tissue function and organogenesis
29
What does the ECM consist of?
* Collagen (fibrillar and non-fibrillar)
* Laminin (basement membrane)
* Perlectan (basement membrane)
* Fibronectin
30
What is collagen
Family of fibrous proteins found in all multicellular organisms
31
Outline the 4 stages of collagen fibre assembly
1. One alpha chain
2. Three alpha chains
3. Collagen fibril
4. Collagen fibre
32
What isthe purpose of covalent cross-links (present in collagen fibres)
Covalent cross-links provide tensile strength and stability
33
What are the main constituents of elastic fibres
Elastic fibres consist of a core made up of the protein **elastin**, and **microfibril**s, which are rich in the protein **fibrillin**.
34
What is laminin?
Ubiquitous, mutli-adhesiuve basement membrane glycoprotein
35
What is fibronectin?
Major connective tissue glycoprotein
36
What is proteoglycan?
Core protein to which one or more glycosaminoglycan chains are covalently attached.
37
List the various fluid comparments in the body
* Intracellular
* Extracellular
* Interstital fluid (between cells)
* Blood plasma
* Transcellular fluid
38
What is the difference between **diffusion** and **osmosis**?
* Diffusion – spontaneous movement of a solute down its concentration gradient until equilibrium
* Osmosis - movement of water down its own concentration gradient. Osmosis moves water toward the area of higher osmolarity & can change cell volume
39
Define **osmolarity**
Osmolarity is a measure of the concentration of all solute particles in a solution.
40
Define **tonicity**
Tonicity defines the “strength” of a solution as it affects final cell volume.
Tonicity depends on:
* cell membrane permeability
* solution composition.
41
List 4 reasons for cellular communication
* Process information - Sensory stimuli (e.g. sight, sound)
* Self preservation - Identify danger & take appropriate actions
* Voluntary movement
* Homeostasis
42
List examples of physiological processes regulated by ionotropic receptors
* The nAChR is involved in skeletal muscle contraction
* The GABAA receptor is important in reducing neuronal excitability
43
Explain the mechanisms of G-protein action in signal transduction and provide examples of physiological processes regulated by G-protein coupled receptors
* Ligand binding initiates a cascade of events including G-protein phosphorylation, uncoupling and target protein activation
* The b-adrenergic (Gas); the a2 adrenergic (Gai) and the AT-1 (Gaq) receptors are examples of G-protein linked receptors
44
Explain the mechanisms of enzyme-linked receptor actions and provide examples of physiological processes regulated by enzyme-linked receptors
## Footnote
* Ligand binding initiates receptor clustering and results in activation of enzymes that are able to phosphorylate target proteins
* The insulin receptor – glucose homeostasis
45
Explain the mechanisms of intracellular receptor actions and provide examples of physiological processes regulated by enzyme-linked receptors
## Footnote
* Either located within the cytosol (Type 1) or the nucleus (Type 2) of a cell and act as transcription factors.
* Type 1 receptors are bound to chaperone molecules & can only translocate following ligand binding and dimerisation
* Glucorticoid receptors – immunomodulation
46
What three cell factors influence cell division?
* Growth factors
* Cell-cell adhesion
* Cell-ECM adhesion
47
Define anchorage dependence
* Cells must be attached to the ECM (a degree of spreading is required) to begin protein synthesis and proliferation (DNA synthesis)
* Attachment to ECM may be required for survival (e.g. epithelia, endothelia) – this is known as anchorage dependence
48
What is an integrin
The most common ECM receptor
49
What are the two major functions of integrins?
* Recognise short, specific peptide sequences
* Recruit cytoplasmic proteins à promote signalling and actin assembly
50
What is the structure of an integrin?
Heterodimer composed of alpha and beta subunits
*The diversity in a and b subunits gives rise to various integrins*
51
What is a focal adhesion
Integrins cluster together to form focal adhesions - these are important for signal transduction (tyrosine phosphorylation)
52
Describe "outside-in" signalling
Signal is from the external environment (of the cell)
* The ECM binds to an integrin complex which stimulates the complex to produce a signal inside the cell
* The composition of the ECM will determine which integrin complexes bind and which signals it receives – this alters the phenotype of the cell
53
Describe "inside-out" signalling
A signal generated inside the cell can act on an integrin complex to alter the affinity of an integrin
54
How do growth factors affect cell division?
In high densities, cells compete for growth factors (which are requried for divison) - this is known as **densitiy-dependent cell divsion**
55
Give an example of a cellular signalling cascade where integrins and growth factors co-operate
ERK MAP kinase cascade
56
What two factors combine to influence cell proliferation
* Growth factors - density dependence cell division
* Integrins - anchorage dependence
The separate pathways act _synergistically_
57
Compare short-term and long-term cell-cell adhesion interactions
* Short-term - transient interactions between cells which do not form stable cell-cell junctions
* Long term - stable interactions resulting in formation of cell-cell junctions
58
What two factors induce cellular locomotion?
* Long-term cell-cell adhesion
* Contact induced spreading
59
Give some example of cell-cell junctions
* adherens junctions
* desmosomes
* tight junctions
* gap junction
60
How is a stable monolayer formed?
## Footnote
*(hint - epithelial cells)*
Contact between epithelial cells leads to the mutual induction of spreading, so that the total spread area of the contacted cells is greater than that of the sum of the two separated cells
This often results in the formation of a stable monolayer
61
What are the components of an adherens junction?
* E-cadherin (calcium-dependent cell-adhesion molecule)
* Catenins (proteins linked to the cytosol)
* alpha
* beta
* gamma
* p120
62
What is the critical step in adherens junction formation?
**Adhesion of E-cadherin with catenins**
*This is mediated by both its extracellular domain and its cytoplasmic tail association*
63
What is the role of MAPK signalling pathways in adherens junction formation
The E-cadherin-mediated adhesion system is subject to outside-in signalling via MAPK signalling pathways
* MAPK signalling --\> activation --\> proliferation
* MAPK off --| proliferation
64
What is the role of β-Catenin in cell-cell adhesion
β-Catenin binds directly to both E-cadherin and α-catenin and plays a critical role in the cell-cell adhesion function of E-cadherin
65
Generally speaking, what is responsible for cellular locomotion?
the major cytoskeleton components - particularly dynein
66
List the various reasons why cells need to be mobile
* Exploit newly created micro-environments
* Evade unfavourable environmental conditions
* Biotic factors
* Abiotic factors
* Cells of vertebrates must move to heal wounds
* Reproduction
67
What is contact inhibition?
* When most non-epithelial cells “collide”, they do not form stable cell-cell contacts, they “repel” one another
* Repuslion by paralysing motility at the contact site, promoting the formation of a motile front at another site on the cell, and moving off in the opposite direction (i.e. contact inhibition)
* Prevents multi-layering of cells
68
What is a likely consequence of a loss of contact inhibtion
* Proliferate uncontrollably (lose density dependence of proliferation)
* Less adherent and will multilayer (lose contact inhibition of locomotion and anchorage dependence)
* Epithelia breakdown cell-cell contacts
* Not Hayflick limited, express telomerase
--\> Cancer
69
Define oncogene
70
Define proto-oncogene
Proto-oncogene = normal cellular gene corresponding to the oncogene
Many components of signal transduction pathways are proto-oncogenes
71
How do cancers spread?
In order to spread to other sites (**metastasis**), cells must:
1. break away from the primary tumour
2. travel to a blood or lymph vessel
3. enter the vessel and lodge at a distant site
4. leave the vessel
5. ultimately establish a secondary tumour
72
What three features must be present for a primary carcinoma to metastasise?
1. Cell-cell adhesion must be down-regulated (e.g. cadherin levels reduced)
2. The cells must be motile
3. Degradation of ECM must take place; matrix metaloproteinase (MMP) levels increased in order to migrate through basal lamina and interstitial ECM
73
What are the three major cytoskeleton proteins
Actin, myosin, intermediate filaments
74
What are microtubules made of?
Tubulin
(hollow cylindrical tube, diameter of ~25 nM)
75
Define the structure of tubulin
Two main types of tubulin (a & b i.e. it is a heterodimer) of around ~ 450 a.a. in length - they display polarity
* a-tubulin contains irreversible nucleotide-binding domain.
* b-tubulin contains reversible nucleotide-binding domains (E-site)
76
How many GTPs does each tubulin subunit bind?
Each subunit binds one molecule of GTP
77
one tubulin subunit consists of?
an single alpha and a single beta subunit
78
Longitudinal tubulin filaments form what kind of structuers?
linear protofilament
79
How many tubulin subunits in a microtubule?
13
80
How do microtubules form?
Lateral interactions between protofilaments
81
What is the difference between T-tubulin and G-tubulin?
Tubulin is a GTPase
* _T Form – GTP bound_, capable of growth – stronger, more stable, can be used as cap
* _G Form – GDP bound_ – weaker, causes curved conformation, allows for refraction
82
Microtubules have polarity - what are the key features of the positive and negative ends?
* Positive End – capable of growing and shrinking (site of adding molecules)
* Negative End – inherently unstable (fraying), stabilised by proteins
83
What is a microtubule catastrophe?
When GTP hydrolysis occurs there is microtubule shrinkage (this is known as a catastrophe)
84
What is microtubule rescue?
If rate of tubulin addition returns to more rapid state, strand begins to grow again - this is known as ‘rescue’
85
What is the role of microtubules in the following structures:
1. Neurones
2. Cilia and Flagella
3. Mitotic spindle
**Neurones**
* Permenant microtubules
* Provide structural support and transportation
* Orientated with positive end towards axon terminal
* *Kinesin* molecules transport ‘cargo’ (e.g. vesicles) towards nerve terminal (anterograde transport)
* *Dyneins* (cytosolic) ® retrograde transport
**Cilia and Flagella**
* Permenant microtubules
* Identical structure to those in nuerones + central bundle of microtubules (axoneme)
* _Axonemes_ have 9+2 structure: 9 doublets surrounding 2 singlets
* _Axonemal dynein_ (within the doublets) - responsible for ‘beating’ & movement (different from neuronal dyneins)
**Mitotic spindle**
* Temporary microtubules
* Mitotic spindle grows outwardly from the centrosome
* _Centrosome_ - microtubule organising centre (MTOC) made of 2 centrioles
* MTOCs align towards opposite poles ® microtubules radiate towards the nucleus
* When growing microtubules ‘meet’ towards the middle ® motor proteins push centrosomes in opposing directions
* Upon binding to centromere ® sister chromatids are pulled apart by ‘catastrophe’ at +ve ends
86
What are the following drugs used for:
* Colchicine
* Vinca alkaloids
* Paclitaxel
* Griseofulvin
* Colchicine - treatment of gout, binds at the intra-dimeric interface
* Vinca alkaloids - treatment of cancer, binds at the inter-dimeric interface inhibiting assembly
* Paclitaxel - adjunct for breast and ovarian cancer, binds to b-tubulin tightly - prevents disassembly
* Griseofulvin - treatment of fundal infections, binds to b-tubulin tightly - prevents disassembly
87
What are intermediate filaments?
Highly dynamic components of the cytoskeleton but are not found in all cells therefore can be used to distinguish between cell types
88
Describe the structure of intermediate filaments
Elongated polymers have a diameter of ~10 nM
89
What are the 5 categories of intermediate filament encoding proteins - which proteins are within these categories?
* Types I & II: Acidic & basic keratins, respectively
* Type III: Vimentin, desmin, GFAP & peripherin
* Type IV: Neurofilaments & internexin (standard), filensin & phakinin (non-standard)
90
Outline the process of intermediate filament assembly
1. Elongated molecules with central α-helical domain which forms a coil-coil with another molecule in the opposite direction
2. Rope-like structure formed by two molecules (staggered tetramer)
3. Filaments join together via associated proteins to form parallel bundles (can also be cross-linked)
91
Outline how intemediate filaments go from monomers to filaments
1. Parallel coiled assembly of two monomers
2. Dimers form staggered anti-parallel tetramers
3. Tetramers aggregate end to end ® protofilament
4. Protofilaments pairs associate laterally ® protofibril
5. 4 associated protofibrils (16 protofilaments) coiled laterally = IF
92
What are the two major classification of IF disorders? Give examples of each
**Laminin Disorders**
* Premature aging syndromes (eg: atypical Werner's syndrome)
* Lipodystrophies (eg: Dunnigan-type familial partial lipodystrophy)
* Myopathies/Neuropathies (eg: Charcot-Marie-Tooth)
**Keratin Disorders**
* Epidermolysis bullosa simplex (EBS)
* Epidermolytic hyperkeratosis
93
What is actin?
Actin - most abundant protein in eukaryotic cells
Flexible linear bundles forming 2D/3D meshworks
94
What are the two major forms of actin?
G-actin globular monomers & F-actin polymers
95
List the 4 major functions of actin
* Form cytoskeleton - determines cell shape
* Create cellular projections like microvilli & filopodia
* Steady elongation - ideal for cellular motility & chemotaxis
* Responsible for phagocytosis & membrane internalisation during endocytosis
96
What is the "barbed end" and the "slow end" of actin? What are their functions?
* Fast-growing plus end = ‘barbed’ end (adds monomers)
* Slow end = ‘plus’ end (releases monomers)
97
In what states can actin exists?
## Footnote
*(hint - remember there is G- and F-actin)*
* G-actin can exist in various ATP-bound states (ATP or ADP but never GTP)
* F-actin exists either as a meshwork, tight parallel bundle or contractile bundle
98
Outline the process of actin polymerisation
Actin is made up of helical polymers – monomers of G-actin (globular), polymerasisation forms F-actin (filamentous)
* ATP-bound G-actin is incorporated into plus end of filament
* Actin – ATPase: hydrolyses ATP
99
Outline the process of actin depolymerisation?
Depolymerisation at minus (‘pointed’) end releases ADP-bound G-actin
This process in known as **treadmilling** and is crucial for actin motility
100
List and describe the major actin binding proteins (ABPs)
* *Nucleators* – eg: **ARP2/3** (actin-related protein) complex – nucleation & triggers branching of actin forming dendritic networks
* *Conformation modulators*
* **Profilin & cofilin** regulate actin dynamics enhancing actin growth & disassembly, respectively
* **CapZ** bind to plus end of actin - act as capping proteins
* *Supramolecular structure organisers* – eg: a-**actinin** - crosslinker that create bundles of actin
* *Membrane anchors* – eg: **Vinculin** links actin to integrins in the cell membrane
101
Define antagonistic pairs (in terms of skeletal muscle)
Antagonist muscle pairs consist of a flexor (eg: bicep) and an extensor (eg: tricep)
102
Define isotonic contraction
Isotonic contraction: muscle changes length ® tension remains the same (there are two types of isotonic contraction – concentric, shortening, and eccentric, lengthening)
103
Define isometric contraction
Isometric contraction: tension develops ® muscle does NOT change length
104
What is the basic composition of a skeletal muscle?
Bundle of muscle cells known as **myofibres**
105
What are myofibres?
* Large & Cylindrical (bundles of muscle cells)
* Multinucleate
* Packed with myofibrils
106
What are the key features of myofibrils?
(inc. the various zones)
* Light & dark bands giving them a ‘striated’ appearance
* A-band: Dark bands, intersected by a darker region --\> H-zone
* I-band: Light bands, intersected by a dark line ® Z-line (Z-disc)
* Z-line: made up of a-actinin & CapZ
* Sarcomere: Functional unit of muscle - lies between two Z-lines
107
What are the key features of the sarcomere?
* **Z-line** - Defines lateral boundaries of sarcomere
* **Actin** - Polymeric thin filament composed of two twisted a-helices - displays polarity
* **Myosin** - Thick filaments - 'motor proteins’. Contain numerous ‘globular heads’ that interact with actin
* **Titin** - Very large ‘spring-like’ filaments anchoring myosin to the Z-line
* **Nebulin** - Large filaments associated with actin
* **Tropomyosin** - Elongated protein bound to actin
* **CapZ & Tropomodulin** - associated with +ve & –ve ends of actin, respectively
108
What is a sarcomere?
Functional unit of muscle - lies between two Z-lines
109
Are cardiac myocytes smooth or striated muscle?
Striated
110
What are intercalated disks?
| (cardiac myocytes)
Intercalated disks:
* Specialised regions connecting individual cardiomyocytes
* Contain numerous gap junctions: allow action potentials to spread rapidly from cell to cell.
111
What two features of myofibres are important for EC coupling
* **T-tubules**: Membrane invaginations that contact the extracellular fluid
* **Sarcoplasmic reticulum** (SR): extensive network of Ca2+-stores surrounding each myofibril
112
Outline the process of EC coupling
1. Action potential (AP) propagates along myofibre membrane (sarcolemma) & T-tubules
2. Depolarisation activates dihydropyridine receptors (DHPR) = conformational change in DHPR
3. This change is transmitted to ryanodine receptors (RyR) on SR = opening of RyR & Ca2+ release from intracellular stores
4. Thus depolarisation = Increase in intracellular Ca2+
113
Compare EC coupling in skeletal and cardiac muscle
Skeletal Muscle
1. AP propagates along sarcolemma & T-tubules
2. Depolarisation activates DHPRs = conformational change in DHPR
3. RyR on SR open = Ca2+ release from intracellular stores
4. Thus depolarisation = increase in intracellular Ca2+® muscle contraction
Cardiac Muscle
1. AP propagates along sarcolemma & T-tubules
2. Depolarisation opens voltage-gated Ca2+ channels (VGCCs) ® Ca2+ influx
3. This Ca2+ has three main effects:
* Ca2+ induced Ca2+ release (CICR) by binding to RyR on SR
* Initiate contraction binding to troponin
* Further depolarisation
4. Thus depolarisation ® increase in intracellular Ca2+® muscle contraction
114
Where do you find smooth muscle?
Present within walls of all hollow organs (e.g. blood vessels, gastrointestinal tract).
115
What is unique about smooth muscle's cytoskeleton arrangement
Does NOT contain regular arrangement of actin & myosin
116
Outlne EC Coupling in smooth muscle
1. Depolarisation activates VGCCs
2. Ca2+-CaM complex ® activates myosin light chain kinase (MLCK)
3. MLCK phosphorylates myosin light chains (MLC20)
4. Cross-bridges with actin filaments = CONTRACTION
117
Outline the various steps involved in the contraction of skeletal muscle
## Footnote
*(starting with the arrival of an AP through to the contraction)*
_Arrival of Action Potential_
1. AP from CNS arrives at motor neuron
2. The action potential is propagated along motor neurone arriving at the neuromuscular junction (NMJ) causing an influx of calcium ions
3. Increased levels of calcium ions cause the release of acetylcholine which diffuses across the synapse binding to receptors on the muscle fibre
_Propagation of AP across Muscle_
1. AP propagates along the muscle membrane and through the T-tubule system of the myofibres
2. Dihydropyridine receptors or Voltage-gated Ca2+ channels located on the T-tubule membrane are activated by the AP and bring about the opening of ryanodine receptors (RyRs)
3. The RyRs are located on the membrane of the sarcoplasmic reticulum (SR) and opening allows Ca2+ efflux from the SR into the myofibre
_Contraction_
1. The rise in Ca2+ within the myofibre initiates contraction
2. At the sub-cellular level calcium binds to troponin C on the actin filament causing troponin T to bind to tropomyosin
3. Formation of the Troponin/Tropomyosin complex (caused by calcium binding) causes a conformational change in the tropomyosin, releasing it from the actin filament – exposing the myosin head binding site
4. ADP phosphorylation and dephosphorylation subsequently allows the myosin heads to pivot and pull the actin filaments towards the centre of the sarcomere
5. The power stroke pulls the actin filaments over the myosin heads, drawing them and the z-discs closer together causing a contraction.
MCD
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