Muscular Physiology Flashcards
Skeletal muscle neurones
Large diameter (10-16µm)
Fast conducting (60-80m/s)
Myelinated
A alpha neurones
Motor unit
The number of muscles controlled by one neurone (10-150 muscle fibres). Motor units responsible for complex movements are usually controlled by one neurone.
Synaptic cleft
20-30nm
ACh receptors at the top of post-junctional folds
Bottom of folds - high concentration of AChE
Acetylecholine formation
- Acetyl-CoA is formed from ATP by the Krebs Cycle
- Choline comes from the breakdown of ACh in the synapse, from the diet and small amounts are made by the liver
- Choline is transported across the nerve cell membrane (the neurolemma) and they combine to form ACh
- Speed of ACh formation is increased by Choline acetyltransferase (ChAT)
Acetylcholine storage
Stored in vesicles in the terminal portion of the motor neurone. Approximately 10,000-12,000 molecules of ACh per vesicle.
Only about 1% of vesicles are immediately available.
Acetylcholine release
- Action potential propagates to the motor end plate
- Action potential opens voltage-gated calcium channels, allowing influx of calcium ions
- Calcium activates SNARE proteins, causing vesicles to move to presynaptic membrane and release ACh into synaptic cleft
- Calcium ions also cause movement of vesicles from reserve pool into immediately available pool
Botox toxicity
Inactivates SNARE proteins so ACh vesicles cannot be released, causing flaccid paralysis
ACh receptor structure
Five subunits, each subunit containing four helical domains
In the adult: two alpha-1, one beta-1, one delta and one epsilon subunit.
ACh binding site
At the interface between the alpha-1 and delta and alpha-1 and epsilon subunits. In order to open the channel, ACh must be bound to both alpha subunits.
ACh receptor function
Ligand-gated ion channel
Allows movement of Na+ and Ca 2+ intracellularly and K+ extracellularly
Predominant flow is Na+ inwards due to strong negative potential inside cell (-90mV)`
Extrajunctional ACh receptors
Found on the muscular membrane, particularly in burns and denervation - pronounced response to NDMAs.
In these receptors, the epsilon subunit is replaced by a gamma subunit.
Presynaptic ACh receptors
Provide positive feedback to the production and mobilization of ACh during repetitive stimulation - responsible for fade during assessment of NMB
ACh binding time
1-2ms
Acetylcholineesterase (AChE)
Catalyses decay of ACh to acetic acid and choline. The choline is reabsorbed into the motor neurone.
Attached to basement membrane by collagen-Q
Anionic site: forms reversible bond with quaternary amide group
Esteratic site: cleaves molecule
Myocyte (muscle fiber): makeup
Made up of multiple sarcomeres (contraction units).
Thick filament
Made up of myosin
Thin filament
Made up of actin. Tropomyosin and troponin are attached to actin. Six actin filaments are attached to the central myosin.
Sarcomere lines
Bounded by two Z lines - structural proteins that anchor actin filaments
Central M disc anchors the myosin
Sarcolemma
Specialized cell membrane for myocyte
T-tubule
Internal projections of the sarcolemma (specialized muscle cell membrane) that facilitates rapid propagation of the action potential throughout the muscle fibre
Sarcoplasmic reticulum
Specialized muscle storage of intracellular calcium
Miniature Endplate Action Potential
1 vesicle of ACh produces a tiny post-synaptic action potential, approx 0.5-1.5 mV. This is the miniature endplate action potential (MEPP).
Excitation-contraction coupling
- When the MEPPs accumulate to 10-15 mV (in reality much more as more ACh is released than required to provide a safety margin), specialized sodium channels open and the action potential is propagated down the muscle fibre
- In the muscle cell T-tubules, a voltage-sensitive dihydropyridine receptor (DHPR) is triggered, undergoing conformational change.
- The DHPR receptor lies very close to the sarcoplasmic reticulum. It activates the ryanodine receptor on the sarcoplasmic reticulum
- The ryanodine receptor releases calcium ions into the sarcolemma, triggering contraction.
SERCA pumps
Pump calcium back into the SR post contraction
SNARE proteins
Bound to both vesicle and presynaptic membrane.
Smooth muscle: differences from skeletal muscle
Not arranged regularly therefore no cross-striations No troponin, only tropomyosin Only one cell nucleus Poorly developed sarcoplasmic reticulum Much fewer mitochondria
Control of smooth muscle
Involuntary by the autonomic nervous system
Visceral smooth muscle is connected by gap junctions that allow calcium waves to cause contraction
Smooth muscle: mechanism of contraction
Unlike skeletal muscle, calcium influx is from the extracellular fluid. No SR.
- Calcium ions enter cells through voltage-gated and ligand-gated channels
- Calcium binds to calmodulin
- Activates calmodulin-dependent light chain kinase
- Catalyses phyosphorylation of myosin
- Activates myosin ATP-ase
- Forms myosin-actin crossbridge and actin slides on myosin
Speed of smooth muscle contration
Slower due to:
- No sarcoplasmic reticulum/t-tubules
- Mechanism is slower
However it lasts longer
Latch-bridge mechanism
Sustained contraction with low energy expenditure. Caused by waiting for myosin to be dephosphorylated by myosin light chain phosphatase
Autonomic nervous system effect on smooth muscle
Parasympathetic tone - increases motility and relaxes sphincters via M3 muscarinic receptors increasing intracellular calcium
Sympathetic tone, via alpha and beta receptors - activate phospholipase C and G-proteins (using cAMP as a second messenger) respectively to reduce intracellular calcium
Nitric oxide and smooth muscle
Nitric oxide (NO) causes relaxation of smooth muscle. It is produced in the endothelium and diffuses into vascular smooth muscle.
It activates guanyl cyclase to catalyse the formation of cGMP from guanosine triphosphate (GTP). This activates protein kinases leading to fall in smooth muscle intracellular calcium.
Smooth muscle differences vs skeletal muscle (ones to know)
Calcium binds to calmodulin rather than troponin C
Source of calcium is extracellular space
Myosin is phosphorylated
