Physiology Flashcards
(156 cards)
1
Q
Physiological functions of skeletal muscles
A
> Posture > Purposeful movement > Respiratory movements > Heat production > Contribution to whole body metabolism
2
Q
Types of muscle tissue
A
There are 3.
- Skeletal muscles
- Cardiac muscle
- Smooth muscles
All capable of developing tension and producing movement through contraction.
3
Q
Skeletal muscle
- appearance
- voluntary?
- neurogenic/myogenic
- source of calcium
- contraction
A
> Striated (dark - myocin - and light - actin - bands)
Voluntary
> Innervated by somatic nervous system
> Neurogenic initiation of contraction
> Motor units
> Neuromuscular junction
> NO gap junctions
> Ca2+ ENTIRELY from sarcoplasmic reticulum
> Motor unit recruitment and summation of contractions = CONTRACTION
Parallel muscle fibres bundled by connective tissue.
Skeletal muscle fibres usually extend the entire length of muscle
Attached to skeleton by tendons
Unbranched
Multinucleate
Fibres are long cylinders - span entire length of muscle
4
Q
Cardiac muscle
- appearance
- voluntary/involuntary
- Neurogenic/myogenic
- source of calcium
- contraction
A
> Striated muscle
Involuntary
Innervated by autonomic nervous system
> MYOGENIC (pacemaker potential) initiation of contraction
> Gap junctions present
> NO neuromuscular junction
> Ca2+ from ECF and Sarcoplasmic reticulum (calcium-induced calcium release)
> Contraction depends on extent of heart FILLING with blood (preload)
5
Q
Smooth muscle
A
> UNstriated
Involuntary muscle
> Autonomic nervous system
6
Q
Are the cytoplasms of nerve cells and skeletal muscle cells continous?
A
NO.
Acetylcholine is the transmitter at Neuromuscular junction
7
Q
What is the neurotransmitter in skeletal muscle?
A
Acetylcholine
Neuromuscular junction
8
Q
What are skeletal muscles organised into?
A
Motor units
9
Q
What is a motor unit?
A
A SINGLE alpha motor neuron and ALL the skeletal muscle fibres it innervates
The axon of the motor neurone branches as it nears its termination and each branch ends in a special type of synapse called the neuromuscular junction.
Myelinated neurone; then it divides into unmyelinated branches near to the muscle.
Indiviudal branches divide further into multiple fine branches, each ending in a TERMINAL BOUTON that forms a chemical synapse with the muscle membrane at the NMJ
10
Q
The number of muscle fibres per motor unit depends on?
A
The functions served by the muscle.
Fine movement = FEWER fibres per motor unit (external eye muscles, facial expression)
Fine Few
More power
Power more important than precision (thighs) = hundreds to thousands fibres per motor unit.
11
Q
A muscle fibre is made up of?
A
Myofibrils
12
Q
What is the FUNCTIONAL unit of muscle fibres?
A
Sarcomere
Thousands of these are placed end to end to form a MYOFIBRILS.
Dozens to hundreds of myofibrils are packed into the muscle fibre like cigarettes in a pack.
13
Q
Muscle fibre = muscle cell
A
just a reminder.
14
Q
Myofibrils/sarcomeres contain
A
Myocin - thick (darker) filaments
Actin - thin (lighter) filaments
15
Q
What structure attaches skeletal muscle to the skeleton?
A
Tendons
16
Q
Each muscle cell (fibre) contains many…
A
myofibrils.
17
Q
General structure of myofibrils
A
Alternating segments of thick and thin protein filaments
Actin and myocin are arranged into SARCOMERES
18
Q
Where can a sarcomere be found? (Z line, m line, h zone, i band)
A
Between two Z-lines
Connect the thin filaments of 2 adjoining sarcomers
19
Q
What are the sarcomere zones?
A
A-band
- Made up of thick filaments along with portions of thin filaments that overlap in both ends of thick filaments
H-zone
- Lighter area within middle of A-band where thin filaments don’t reach
M-line
- Extends vertically down middle of A-band within the centre of H-zone
I-band
- Consists of remaining portion of thin filaments that do not project in A-band
20
Q
How is muscle tension produced?
A
By sliding of actin filaments on myosin filaments
Force generation depends upon ATP-dependent interaction between thick (myosin) and thin (actin) filaments
21
Q
ATP is required for both…
A
Contraction and relaxation of skeletal muscle
during muscle contraction to power cross bridges
During relaxation to release cross bridges; to pump Ca2+ back into the sarcoplasmic reticulum
22
Q
Excitation contraction coupling
A
Process whereby the surface action potential results in activation of the contractile structures of the muscle fibre
23
Q
Ca2+ release in skeletal muscle
A
In skeletal muscle fibres, Ca2+ is released from the LATERAL SACS of the sarcoplasmic reticulum, when the surface acton potential spreads down the transverse (T) tubules.
24
Q
Where is Ca2+ released from in skeletal muscle?
A
The lateral sacs of the sarcoplasmic reticulum
when the surface action potential spreads down the transverse (T) tubules.
25
What structure does the action potential have to travel down in order for calcium to be released?
T (transverse) tubules
26
What are T tubules?
Transverse tubules (T-tubules) are extensions of the sarcolemma (muscle cell membrane) that penetrate into the centre of skeletal and cardiac muscle cells.
27
Calcium is needed...
> Switch on cross bridge formation
> Ca2+ is the link between excitation and contraction
> Ca2+ is entirely derived from sarcoplasmic reticulum in skeletal muscle
28
Rigor mortis
In absence of ATP - stiffness can occur .
29
Magnesium ATPase? Myosin ATPase??
-- questions
30
Gradation of skeletal muscle tension (strength of contraction) depends on...
Two primary factors.
1. Number of muscle fibres contracting within the muscle
- MOTOR UNITS allow simultaneous contraction of a number of muscle fibres
- a stronger contraction could be achieved by stimulation of more motor units - MOTOR UNIT RECRUITMENT
- Asynchronous motor unit recruitments during sub maximal contractions helps prevent muscle fatigue
2. Tension developed by each contracting muscle fibre
- depends on FREQUENCY of stimulation and SUMMATION of contractions
- LENGTH of muscle fibre at the onset of contraction
- Thickness of muscle fibre
31
Stimulation of more motor units is called..
Motor unit recruitment
32
In skeletal muscle, the action potential is..
Much SHORTER than the duration of the resulting TWITCH.
Possible to summate twitches to bring about a stronger contraction through repetitive fast stimulation of skeletal muscle.
33
Summation of twitches
Brings about a stronger contraction through repetitive fast stimulation of skeletal muscle.
34
What is a "twitch"
A single contraction
35
If a muscle fibre is restimulated after it has completely relaxed, the second twitch is....
the same magnitude as the first
36
If a muscle fibre is restimulated BEFORE it has completely relaxed, the second twitch is...
ADDED onto the first twitch
Resulting in SUMMATION
37
Tetanus
If a muscular fibre is stimulated so rapidly that it does not have an opportunity to relax at all between stimuli, a maximal SUSTAINED contraction occurs i.e. TETANUS
38
the tension developed by skeletal muscle increases with...
increasing FREQUENCY OF STIMULATION
39
Increased the frequency of stimulation is an important mechanism for..
MODULATING the force of contraction in skeletal muscle.
40
When can maximal titanic contraction be achieved?
When the muscle is at its OPTIMAL LENGTH before onset of contraction.
41
Developed tension depends on
The initial length of the skeletal muscle fibres
42
What is the optimum length of muscle
lo
Point of optimal overlap of thick filament cross bridges and thin filaments cross bridge binding sites.
Maximal titanic tension can be achieved.
i.e. its RESTING length
43
Two types of skeletal muscle contraciton
1. Isotonic contraction
| 2. Isometric contraction
44
Isotonic contraction
Used for 1) body movements and 2) moving objects.
Muscle TENSION remains constant as the muscle length changes
Tension = constant
Length = changes
45
Isometric contraction
Used for 1) Supporting objects and 2) maintaining body posture
Muscle tension develops at constant muscle length
Tension = changes
Length = constant
46
The velocity of muscle shortening decreases as the load...
Increases
47
Each motor unit usually contains...
One type of muscle fibre.
48
Metabolic pathways that supply ATP in muscle fibres (3)
1. Transfer of high energy phosphate from creatine phosphate to ADP - immediate source of ATP
2. Oxidative phosphorylation - main source when O2 is present
3. GLYCOLYSIS - main source when O2 is NOT present.
49
3 types of muscle fibres
1. Slow oxidative type 1 (slow twitch)
2. Fast oxidative Type IIa (intermediate twitch fibres)
3. Fast glycolytic Type Iix fibres (fast twitch muscle fibres)
50
Slow oxidative type I fibres
> when are they used?
> types of metabolism used
(aerobic/anaerobic)
(slow-twitch fibres)
are used mainly for prolonged relatively low work aerobic activities e.g. maintenance of posture, walking
resistant to fatigue
"red" fibres
51
Fast oxidative type IIa fibres
> when are they used?
> types of metabolism used (aerobic/anaerobic)
Intermediate-twitch fibres
use both aerobic and anaerobic metabolism and are useful in prolonged relatively moderate work activities e.g. jogging
52
Fast Glycolytic Type IIx
> when are they used
> type of metabolism used
fast-twitch fibers
use anaerobic metabolism and are mainly used for short-term high intensity activities e.g. jumping
fatigue quickly.
"white" fibres
53
what is a reflex?
A stereotyped response to a specific stimulus
54
Stretch reflex is what kind of reflex?
Monosynaptic spinal reflex
55
Stretch reflex
- negative feedback
- posture
Negative feedback that resists passive change in muscle length to maintain optimal resting length of muscle
Helps maintain posture.
The sensory receptor is the muscle spindle and is activated by muscle stretch
Stretching the muscle spindle increases firing in the afferent neurons
The afferent neurons synapse in the spinal cord with the alpha motor neurons (efferent limb of the stretch reflex) that innervate the stretched muscle
Activation of the reflex results in contraction of stretched muscle
56
Muscle spindle
- what is it
- activated by?
what are the sensory nerve endings known as?
The sensory receptor.
Collection of specialised muscle fibres
AKA Intrafusal fibres
Found within BELLY of muscles and run parallel to ordinary muscle fibres (extrafusal fibres)
Sensory nerve endings = ANNULOSPIRAL fibres.
Have their own efferent (motor) nerve supply
Efferent neurons that supply muscle spindles are called GAMMA MOTOR NEURONS
Activated by muscle stretch
Stretching the muscle spindle increases firing in the afferent neurons
57
Stretching the muscle spindle does what?
Increases firing in the afferent neurons
58
In the stretch reflex, where do the afferent neurons synapse?
What do the synapse with?
In the spinal cord
synapse with the alpha motor neurons (efferent limb of the stretch reflex) that innervate the stretched muscle
Activation of the reflex results in contraction of stretched muscle.
59
How can the stretch reflex be elicited?
By tapping the muscle tendon with a rubber hammer.
This rapidly stretches the muscle resulting in its contraction
60
Knee Jerk
> Spinal segment
> Peripheral nerve
L3, L4
Femoral nerve
61
Ankle jerk
S1, S2
TIbial nerve
62
Biceps jerk
C5-C6
Radial nerve
63
Triceps jerk
C6-C7
Radial nerve
64
Sensory nerve endings of muscle spindles are known as?
Annulospiral fibres
65
What are normal muscle fibres also known as?
Extrafusal fibres.
66
Discharge from the muscle spindles sensory endings Increases as the...
muscle (and hence spindle) is stretched.
67
Ɣ motor neurons
Adjust level of tension in the muscle spindles to maintain their sensitivity when the muscles shorten during muscle contraction
Gamma motor neurons are efferent neurons that supply muscle spindles.
68
Does the contraction of intrafusal fibres contribute to the overall strength of muscle contraction?
No it does not.
69
Intrinsic Muscle Disease
Genetically determined myopathies
Congenital myopathies: characteristic microscopic changes leading to reduced contractile ability of muscles
Chronic Degeneration of contractile elements - muscular dystrophy
Abnormalities in muscle membrane ion channels e.g. myotonia
Acquired myopathies
Inflammatory myopathies e.g. polymyositis, inclusion body myositis
Non-Inflammatory myopathies e.g. fibromyalgia
Endocrine mypoathies e.g. Cushing syndrome, thyroid disease
Toxic myopathies e.g. alcohol, statins
70
Symptoms of muscle disease
> Muscle weakness/tiredness
> Delayed relaxation after voluntary contraction (myotonia)
> Muscle pain (myalgia)
> Muscle stiffness
71
Electromyography
Electrodes detect the presence of muscular activity
Records frequency and amplitude of muscle fibres action potentials
EMG findings not pathognomonic of specific disease - will not provide the definitive diagnosis
EMG helps differentiate primary muscle disease from muscle weakness caused by neurological disease
Nerve conduction studies usually done at the same time as an EMG
72
Nerve conduction studies
Determine the functional integrity of peripheral nerves
73
Muscle enzymes
Creatine kinase
74
Inflammatory markers
C reactive protein (CRP)
Plasma viscosity
75
Investigations for neuromuscular disease
> Electromyography
> Nerve conduction studies
> Muscle enzymes
> Inflammatory markers
> Muscle biopsy
76
3 types of joint
Synovial
Fibrous
Cartilaginous
77
Fibrous joint (synarthrosis)
> Bones united by fibrous tissue
> Doesn't allow any movement
> Bones of the skull in adults
78
Cartilaginous joint (Amphiarthrosis)
> Bones united by cartilage
> Allow limited movement
> Examples - intervertebral discs; pubic symphysis ; part of sacroiliac joint; costochondral joints
79
Synovial joints (Diarthrosis)
> Bones separated by a cavity (containing synovial fluid) and united by a fibrous capsule
> Synovial membrane
> Articular surfaces are covered with cartilage.
80
Classifications of synovial joints
1. Simple - one pair of articular surfaces (metacarpophalangeal joint)
2. Compound synovial joint (more than one pair of articular surfaces) - elbow joint
81
The inner aspect of the fibrous capsule is line with?
Synovial membrane
82
Synovial membrane
- what is it
- what does it contain
Vascular connective tissue with capillary networks and lymphatics.
Contains SYNOVIAL CELLS (fibroblasts) which produce synovial fluid
83
Synovial cells
Fibroblasts
Produce synovia fluid
84
Role of joints during purposeful motion
> Stress distribution
> Confer stability
- shape of the articular component
- ligaments
- synovial fluid acts as an adhesive seal that freely permits sliding motion between cartilaginous surfaces
> Joint lubrication
- cartilage interstitial fluid
- synovial membrane derived hyaluronic acid (mucin)
- Synovial membrane-derived lubricin
85
Upon what is the greatest share of loading energy?
Muscles and tendons.
86
Hyaluronic acid
Mucin
Disaccharide polymer
Joint lubrication.
Derived form synovial membrane
87
Lubricin
Derived from synovial membrane
Glycoprotein
Joint lubrication
88
Synovial fluid
- functions
> Lubricates joint
> Facilitates joint movements (reduce friction --> minimise wear and tear)
> Aids in nutrition of articular cartilage
> Supplies the chondrocytes (cartilage cells) with O2 and nutrients
> Removes CO2 and waste products
89
Is synovial fluid a static poole?
No, it is continuously replenished and absorbed by the synovial membrane
90
Why is synovial fluid viscous?
Due to the presence of hyaluronic acid (mucin)
91
Viscosity and elasticity of the synovial fluid varies with...
Joint movement
92
What cells are present in synovial fluid?
Mononuclear leukocytes
| very few
93
Rapid movement does what to synovial fluid?
Decreases its viscosity
Increases its elasticity
these properties become defective in a diseased joint e.g. in osteoarthritis.
94
Gross appearance of synovial fluid
Cell count
Clear & colourless.
<200 WBC/mm^3
in inflammatory and septic arthritis, WBC count increases.
Synovial fluid turns red in traumatic synovial tap and in haemorrhagic arthritis
95
Why would synovial fluid be red?
Due to trauma
Haemorrhagic arthritis
96
Normal Synovial Fluid
Viscosity = high
Colour = Colourless
Clarity = transparent
Total WBC/mm^3 = <200
PMN leukocytes/mm^3 = <25
97
Inflammatory synovial fluid
Viscosity = Low
Colour = Straw/yellow
Clarity = translucent
Total WBC/mm^3 = 2000-75000
PMN leukocytes/mm^3 = often >50
98
Septic synovial fluid
Viscosity = Variable
Colour = Variable
Clarity = Opaque, milky
Total WBC/mm^3 = often>100,000
PMN leukocytes/mm^3 = often >75
99
Articular (hyaline) Cartilage
- function
> Low friction lubricated gliding surface. Helps prevent wear and tear.
> Distributes contact pressure to subchondral bone
> Composition of cartilage extracellular matrix and the interaction between the fluid and solid phase of the cartilage plays a significant role in determining the mechanical properties of cartilage
----
Elastic and sponge-like properties
Covers articular surfaces of bones
Has ECM made from WATER (70%), COLLAGEN (20%) - mainly type II contributes to elastic behaviour of cartilage.
PROTEOGLYCANS (10%)
100
Structure of articular cartilage
From most superficial to deepest.
> Articular surface
> Superficial zone (includes articular surface) - 10-20%
> Middle zone (40-60%)
> Deep zone (30%)
> Calcified zone
> Subchondral bone
Chondrocytes present in each zone (not in subchondral bone)
Zones differ in ORGANISATION OF COLLAGEN FIBRES and RELATIVE CONTENT OF CARTILAGE COMPONENTS
101
Which type of collagen is found in articular cartilage (for the most part)?
Type II collagen
finer than type I
Forms 3 dimensional mesh work
Contributes to elastic behaviour
102
Articular cartilage - mechanical properties of water.
70% of cartilage wet weight.
Unevenly distributed - highest near articular surface. (80%)
Cartilage content decreases with age
Maintains resiliency of the tissue and contributes to the NUTRITION and lUBRICATION system
103
Articular cartilage - mechanical properties of COLLAGEN
> 20% of wet weight
> Mainly type ii collagen (decreases with age)
> Maintains cartilage architecture
> Provides tensile stiffness and strength
104
Articular cartilage - mechanical properties of PROTEOGLYCAN
> 10% cartilage wet weight
> Highest conc. is found in MIDDLE and DEEP zones
> Composed mainly of GLYCOSAMINOGLYCAN (chondroitin sulphate, keratin sulphate ) - GAGs
> These GAGs are bound to a core protein and often linked to hyaluronan
> Chondroitin decreases with age
> Responsible for compressive properties associated with LOAD BEARING
105
What makes up over 98% of the cartilage volume?
Extracellular matrix
106
ECM of articular cartilage
Synthesised, organised, degraded and maintained by CHONDROCYTES (less than 2% of total cartilage volume)
Articular cartilage is AVASCULAR and the chondrocytes receive nutrients and O2 via synovial fluid
Normal joints: Degradation does not exceed rate of replacement
107
Negative factors/degradative factors in cartilage
Mettaloproteinase
Proteolytic enzymes - collagenase, stromelysin
108
Changes in the relative amounts of the three major components of cartilage would...
Change the mechanical properties of the cartilage.
Joint disease would also occur if the rate of ECM degradation EXCEEDS the rate of its synthesis
109
Catabolic factors of cartilage matrix turnover
Enhance degradation.
Stimulate proteolytic enzymes and inhibit proteoglycan synthesis.
- TNFα
- Interleukin 1
110
Anabolic factors of cartilage matrix turnover
Stimulate proteoglycan synthesis and counteract effects of IL-1
- Tumour growth factor (TGF β)
- Insulin-like growth factor (IGF-1)
111
MARKERS of cartilage degradation
> Serum & synovial keratin sulphate
-- increased levels indicate cartilage breakdown
-- level increases with age and patients with osteoarthritis
> Type II collagen in synovial fluid
-- increased levels indicate cartilage breakdown
-- evaluating cartilage erosion (osteoarthritis and rheumatoid arthritis)
112
What causes rheumatoid arthritis
Synovial cell proliferation and inflammation
113
Osteoarthritis - general cause
Cartilage and synovial composition and function deteriorate with age and repeated wear and tear
114
Gouty arthritis
Deposition of salt crystals
Uric acid crystals
115
Soft tissue rheumatism
Injury and inflammation to periarticular structures causes this.
Injury to tendon leading to tendonitis.
116
Effects on subchondral bone following cartilage wear and tear
Cyst formation
Osteophyte formation (bony spurs)
Sclerosis in subchondral bone
Thickened capsule
Fibrillated cartilage
Synovial hypertrophy
117
Gout
Deposition of needle shaped uric acid crystals
--> gouty arthritis
118
Pseudo-gout
Deposition of rhomboid shaped calcium pyrophosphate crystals causes pseudo-gout.
119
In skeletal muscle cell fibres - where are the nuclei
Periphery of the fibre
Cardiac muscle on the other hand, has their nuclei in the centre of the cell.
120
What are muscle fibres grouped into? (F)
Bundles called FASCICLES.
A muscle contains several fascicles.
121
Epimysium
Connective tissue that surrounds the muscle as a whole
122
Perimysium
Connective tissue around a single fascicle.
123
Endomysium
Connective tissue around a single muscle fibre.
124
Cell found in cartilage
Chondrocytes (chrondroblasts when immature)
125
Where are chondrocytes located?
Within a space in the ECM called a LACUNA.
126
Lacuna
Structure that houses Chondrocytes
also house osteocytes
127
Types of cartilage
> Hyaline cartilage (looks blue-white in colour and is translucent)
> Elastic cartilage
> Fibrocartilage
- hybrid between tendon and hyaline cartilage.
- bands of densely packed type I collagen
- chondrocytes
- surrounded by small amounts of cartilaginous ECM
- white
128
Haemopoiesis
- in utero and babies
- early twenties
Blood cell production
Begins in the BONE MARROW well before birth and by birth marrow is the site of haemopoesis
By early twenties, AXIAL and LIMB GIRDLE skeleton involved in blood production
129
Composition of bone (histology lecture)
> 23% collagen
> 2% non-collagen
> 10%water
> 65% bioapatite (form of calcium phosphate - hydroxyapatite)
130
Cortical bone
Makes up the shaft (diaphysis)
Hard shit
131
Cancellous/trabecular/spongy bone
Occupies the ends of bone (epiphyses).
Fine meshwork of bone - looks like an Aero bar
Made of little tiny struts of bone forming a 3D matrix
LACKS haversian canals.
132
Both types of bone are...
LAMELLAR (made up of layers)
133
Osteon
Concentric circles of bone surrounding a canal
134
Haversian canal
Microscopic tubes that allow blood vessels and nerves to travel through them
Surrounded by osteon
135
Volkmann's canal
Canals that run between haversian canals
136
Osteoprogenitor cells
Located on bone surfaces. (e.g. under the periosteum)
| - serve as a pool of reserve osteoblasts
137
Osteoblasts
Bone forming cells found on surface of developing bone.
Plentiful RER and prominent mitochondria
138
Osteocytes
Bone cell trapped within the bone matrix
139
Osteoclasts
Large multinucleate cells.
Found on the surface of bone and are responsible for bone resorption
140
Bone remodelling - Cutting cone
Osteoclasts will congregate and drill into the bone - tunnel
Blood vessel will grow into the tunnel, with osteoblasts which lay down new lamellar bone
Process continues until only the space of a Haversian canal remains
Collection of osteoclasts/blasts that participate in this process = BASIC MULTICELLULAR UNIT (BMU)
141
Bone mineralisation
Osteoblasts secrete:
Collagen
Glycosaminoglycans (GAGs)
Proteoglycans
+ other organic components
collectively called osteoid
Bone made up of calcium phosphate crystals (hydroxyapatite)
142
Younger osteons often...
obliterate older osteons
143
Woven bone
The type/pattern of bone laid down after a break.
Collagen fibres are laid down in a haphazard fashion.
Not as strong.
Subsequently remodel into lamellar bone by being broken down by osteoclasts and reformed by new osteoblasts.
144
Terminal Bouton
- what is it surrounded by/
Individual branches of motor neurone axon further divide into multiple fine branches, ending in a terminal bouton.
Forms a chemical synapse with the muscle membrane at the NMJ
Release of Acetylcholine (ACh)
- Surrounded by Schwann cell.
145
α-Motoneurone
> Cell body in ventral horn of spinal cord (or brain stem)
> Myelinated axon
> Unmyelinated axon terminals (ending in terminal bouton)
> Presynaptic terminal bouton synapse at the ENDPLATE region of skeletal muscle fibre
146
Skeletal Neuromuscular Junction
- key features
1) Terminal bouton (and surrounding Schwann cell)
2) Synaptic vesicles
3) Synaptic cleft
4) End plate region of the sarcolemma
Synaptic vesicles (containing ACh) cluster at ACTIVE ZONES
Nicotinic ACh receptors are located at regions of the junctional folds that face the active zones
147
Synaptic transmission at the skeletal neuromuscular junction
1. Choline + Acetyl CoA --> CAT (choline acetyl transferase) = ACh
2. ACh is actively accumulated in vesicles by specific ACh transporter
3. Calcium concentration rises and binds to specific proteins on vesicle membrane.
4. Release ACh cargo into the cleft and diffuses to post synaptic membrane
5. Activate post junctional nicotinic ACh receptors.
6. Acetylcholinesterase hydrolyses ACh into choline and acetate
Acetate diffuses out of the cleft.
148
Neuromuscular Junciton - Pre-synaptic processes
> Choline is transported into the terminal by the choline transporter (symport with Na+)
> ACh is synthesised in the cytosol from choline and acetyl coenzyme A (acetyl CoA – supplied by mitochondria) by the enzyme choline acetyltransferase (ChAT, or CAT)
> ACh is concentrated in vesicles by the vesicular ACh transporter
> Arrival of the action potential at the terminal (1) causes depolarization and the opening of voltage-activated Ca2+ channels (2) allowing Ca2+ entry to the terminal (3)
> Ca2+ causes vesicles ‘docked’ at active zones to fuse with the presynaptic membrane (exocytosis) – ACh diffuses into the synaptic cleft (4) to activate post-synaptic nicotinic ACh receptors in the endplate region (5)
149
Neuromuscular junction - Post-synaptic processes.
> ACh activates nicotinic ACh receptors located at the muscle end plate.
> Nicotinic ACh receptors (pentamer)
- opens when 2 molecules of ACh bind to exterior of receptor.
> Open channel is roughly equally permeable to Na+ and K+
> When the gate is open Na+ enters the muscle cell (influx) whilst K+ exits (efflux) simultaneously through many receptors at the ned plate
Influx of Na+ is greater than for K+ - END PLATE POTENTIAL (E.P.P.) is generated.
------
150
Structure of Nicotinic ACh receptors at post synaptic membrane
Pentameric
Glycoprotein subunits that surround a central, cation selective, pore (formed by five M2 helices)
Opens when 2 molecules of ACh bind to the exterior of the receptor
(alpha, gamma, alpha, beta, delta - clockwise)
151
Post synaptic processes (2) Electrical responses to Synaptically released ACh at end plate.
> ACh is stored and conenctrAted in vesicles
> Each vesicle contains a "quantum" of neurotransmitter
> Elctricial response to ONE quantum of transmitter is a MINITURE ENDPLATE POTENTIAL (m.e.p.p.)
> Many m.e.p.ps summate to produce end plate potential - a graded electrotonic response
> An e.p.p. that exceeds threshold triggers "all or none" propagated action potential that initiates contraction.
152
End plate potential (e.p.p) triggers....
Opening of voltage activated Na+ channels causing a muscle action potential (AP)
1 AP in motor nerve triggers one AP in the muscle --> TWITCH
153
How does an action potential propagate alongna muscle?
Muscle fibre has voltage activated Na+ channels.
AP propagates from the endplate over the length of the muscle fibres.
154
How does the muscle action potential cause contraction?
Release of Ca2+ from intracellular stores.
AP propagates over the surface membrane of skeletal muscle fibre and enters T tubules
AP arriving at T tubule triggers release of Ca2+ from the sarcoplasmic reticulum --> contraction
155
Termination of ACh action
Done by Acetylcholinesterase.
Hydrolysis of ACh to from choline and acetate
Choline taken up by choline transporter
Extremely efficient enzyme. Virtually all ACh molecules are hydrolysed once they unbind from receptor.
156
Cement lines
The lines that are often visible surrounding the osteon are termed cement lines.
These are only found in osteons that have formed during remodelling (so not in original development).
