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Physiology 3120 Lecture Notes - Neuromuscular Junction, Suxamethonium Chloride, Neostigmine

Course Code
Tom Stavraky

of 2
Human Physiology
Monday, October 5, 2009
Neuromuscular Junction
RMP in muscle cells is -90mV
Sequence of events in neuromuscular transmission
1. Action potential in alpha-motor nerve
2. Depolarization of alpha-motor nerve terminal
3. Voltage-gated calcium channels open
4. Influx of calcium
5. Movement of calcium causes fusing of ACh vesicles to membrane terminal, and releases ACh in
quantal amounts
6. Diffusion of ACh to muscle cell membrane endplate
7. Attachment of ACh to nicotinic ACh receptors at endplate
8. Opening of non-specific cation channels (ligand-gated channels)
Increased conductance of both sodium & potassium
Preferential influx of sodium because RMP of muscle cell is at the equilibrium potential
for potassium
9. Preferential influx of sodium into muscle cell
10.Depolarization of muscle cell membrane at the endplate (endplate potential [EPP]) no AP yet
11.Local currents open voltage-gated sodium & potassium channels on membrane adjacent to
endplate production of AP
12.AP propagates outward in all directions along muscle cell
Muscle cells not myelinated
13.ACh broken down to choline & acetate by acetylcholinesterase
The enzyme is found on the basement membrane
1 AP in alpha-motor nerve = 1 AP in muscle cell membrane
Evidence for the action of ACh at the NMJ
1. EPP prolonged by inhibition of acetylcholinesterase (i.e. neostigmine)
Prevent ACh from breaking down; better chance of finding a receptor and gates stay
open longer
2. EPPs are inhibited by ACh receptor competitors (i.e. succinylcholine)
3. Exogenous (external sources of) ACh causes EPPs
4. If ACh is depleted, EPPs are reduced
Contraction of Skeletal Muscle
Structure of skeletal muscle
Whole muscle fascicle muscle cell myofibril myofilaments (thick & thin; together,
make the sarcomere)
Number of muscle cells in a whole muscle depends on the size of the muscle
Length of muscle cells vary from few mm to 12cm long
Contain glycogen, lipids for energy, and myoglobin to store oxygen
Strength of muscle
Pound-for-pound, the uterus is the strongest muscle in the body
Overall, the gluteus maximus or the quadriceps is the strongest muscle in the body
Sarcoplasmic reticulum
T-tubules (continuous with cell membrane) deliver APs down into the myofibril
The parts of the SR that are up against the T-tubules are called the lateral sacs, or terminal
Thin myofilament/actin
G-actin (globular)
Polymerized into a two-stranded alpha-helical chain; contains myosin binding sites
Rod-shaped protein
Two alpha-helical polypeptide chains wrapped together
In relaxed muscle, tropomyosin situated so that it partially covers myosin binding sites
Comprised of 3 chains
Troponin C = calcium
Troponin A = action
Troponin T = tropomyosin
Thick myofilament
Made of myosin
2 long polypeptide strands, each forming part of the tail, hinge, arm, and 1 head
Each head also contains an ATP binding site, and an actin binding site
Sarcomere is the smallest functional unit of the muscle sarcomere
A-band (dark region on micrograph because more protein) is the length of the myosin
I-band is only the actin filaments
Z-discs are the boundaries between adjacent sarcomeres