Neuromuscular physiology Flashcards
How are cholinergic receptors subdivided?
Nicotinic receptors
- can be artificially stimulated by nicotine (found in tobacco)
Muscarinic receptors
- can be artificially stimulated by muscarine from the poisonous amanita mushroom
What are nicotinic receptors?
Transmembrane proteins with five subunits (2 alpha, beta, epsilon (gamma in fetus), delta) that surround a Na+ ion channel. This is an example of a ligand-gated ion channel.
What are muscarinic receptors
Predominantly found at PSNS postganglionic junctions and work instead by G-protein linkage
Where do nicotinic receptors exist in the body?
- Throughout the CNS
- Somatic nervous system: neuromuscular junction
- Autonomic ganglia
- Adrenal medulla
Where are the Ach binding sites on the nicotinic receptor
On the alpha subunits
Describe how the arrival of an action potential at a neuromuscular junction leads to muscle contraction
AP arrives at NMJ –> synaptic vesicles containing Ach exocytose on the pre-synaptic terminal of the NMJ –> Ach enters the synaptic cleft –> Ach bind to alpha subunits of the nicotinic receptors on the postsynaptic membrane –> conformational change and opening of Na + channels on the post-synaptic membrane –> Influx of sodium through the sarcolemma–> increases the membrane potential of the sarcolemma until action potential threshold is reached –> an action potential is generated and propogated down the sarcolemma and down T-TUBULES (extensions of the muscle cell membrane into the cell) and into the sarcoplasmic reticulum –> Release of calcium –> actin-myosin cross-bridge formation and myofibril shortening = muscle contraction.
Classify nerve fibers with their diameter, velocity and innervation.
A alpha 15 um 100 m/s Motor, proprioception
A beta 10 50 m/s Touch, pressure
A gamma 5 25 m/s Muscle spindles
A delta 3 20 m/s Pain, temp, touch
B 2 10 m/s Pre-ganglionic ANS
C 1 1 m/s Pain, postganglionic SNS
What is myelin?
Protein-lipid complex
Formed by layers of plasma membrane derived from Schwann cells. Myelin extends along the axon interrupted by Nodes of Ranvier
What is the function of myelin and nodes of Ranvier?
Myelin insulates the nerve from the extracellular fluid except at the Nodes of Ranvier.
Action potentials jump from one node to the next in a process known as saltatory conduction
What are the advantages of saltatory conduction
- Faster conduction velocity
2. Conservation of energy
What is the resting membrane potential of neurons and how is this generated
-70 mv. The interior is negative compared to the exterior.
This is generated by the Na-K ATPase pum: pumps sodium out and K in against their concentration gradients
Why is the outside of the cell positive relative to the inside?
Na-K ATPase has a coupling ratio of 3/2 meaning that for every 3 positive Na ions moved out, only 2 K+ are moved in. This means that the outside of the cell is contains more positive charge. This accounts for part of the resting membrane potential of -70mV
What is the main contributor to the negative resting membrane potential
The neuronal cell membrane is slightly permeable to K+ ions. This means that K+ ions leak from the inside of the cell to the outside of the cell making the outside of the cell even more positive relative to the inside of the cell
What are the two factors the create the resting membrane potentail
- Main factor - neuronal cell membrane slight permeability to K+ ions leading to positive charge accumulating outside the cell relative to inside of cell
- Na-K ATPase has a coupling ratio of 3/2 which means that for every 3 Na+ ions moved out of the cell there are only 2 K+ ions moved into the cell contributing to the charge difference that exists = resting membrane potential
What contributes to 75% of energy utilized by nerve cells?
Na-K ATPase pump
How long does a nerve cell action potential last?
about a millisecond
What is the “all or none” law?
Once threshold potential is reached the magnitude and duration of the action potential is constant regardless of the strength of the stimulus
What happens when membrane threshold is reached?
Depolarization occurs
- Voltage-gated ion channels open and membrane permeability to Na ions increases suddenly. Na rapidly moves down its concentration gradient from the outside of the cell to the inside changing the membrane potential from -70 mV to + 40 mV
What happens when the membrane potential reaches +30 mV
Voltage-gated K+ channels open –> K+ ions now rapidly move to the outside of the membrane –> this is called REPOLARIZATION which positively charges the outside of the membrane relative to the inside of the membrane once again
What takes place during the refractory period
The Na-K ATPase pump rapidly re-establishes the resting membrane potential
What is a motor unit
The axon of one motor neuron branches as it enters the muscle, and control the activity of a variable number of muscle fibres. One motr neuron and the muscle fibres it controls is called a motor unit
What determines the number of muscle fibres controlled by one motor neuron within one motor unit?
Fine delicate movements e.g. extrinsic muscles of the eye have 6 - 10 muscle fibres are supplied by a single motor neuron
Fine control not required e.g. gastrocnemius motor unit can contain up to 2000 muscle fibres
Describe the events within the pre-synaptic nerve terminal at the arrival of the action potential
AP arrives –> Voltage gated Ca2+ channels open –> exocytosis of the synaptic vesicles containing Ach into the synaptic cleft. The synaptic vesicles are concentrated near ACTIVE ZONES
Where are the nicotinic receptors concentrated on the post-synaptic membrane?
in crests which align with pre-synaptic active zones
What is the function of the junctional folds in the post-synaptic membrane
Junctional folds contain high concentrations of acetylcholinesterase –> breakdown of Ach
Which binging sites on the Ach receptor must be occupied for activation of the receptor
Both alpha subunits
What happens when the nicotinic receptor is activated
The ion channel opens and many Na+ move down their concentration gradient into the cell and a few K+ ions move down their concentration gradient out of the cell
Describe the acetylcholine cycle at the synapse
Acetylcholine is rapidly metabolized by acetylcholinesterase in the synaptic cleft forming choline and acetate. choline is then transported back into the pre-synaptic terminal where it is combined with acetyl coA to form acetylcholine plus CoA. acetylcholine is then packaged into synaptic vesicles and transported to the active sites for release. choline can also be synthesized de novo in the neurone
Describe the structure of skeletal muscle
Skeletal muscle is made up of multiple bundles of muscle fibres (100 - 1000 um). Each muscle fibre (10 -100um) is surrounded by the cell membrane called the sarcolemma. Each muscle fibre is made up of multiple myofibrils (1 um). Each myofibril is made up of multiple filaments containing a thin and a thick component. Each myofibril consists of repeating units called sarcomeres.
Regarding the sarcomere: what are A-bands and what are I bands
What is the Z line
What is the M line
What is the H zone
When viewed under polarized light, muscles myofibrils have alternating dark and light zones. The regions that appear dark area called anisotropic = A-bands. The light regions are called isotropic = I-bands.
Z-line - connection between actin filaments in separate sarcomeres
M-line - attachment site for myosin (thick) filaments - centre of the A band and centre of the sarcomere
H-zone - Region in the middle of the sarcomere where there is no actin myosin overlap - contains the M-line
What is a Z-line?
Each I-band is divided by a characteristic line called a Z-line. The space between adjacent Z-lines is called a sarcomere
What is contained within the darker A bands?
Myosin - thick filaments
What makes up the I-bands?
Actin - thin filaments arranged in a double helix arrangement
What is the name of the other proteins arranged between the grooves of the actin
Tropomyosin. Molecules of troponin are arranged at intervals along the tropomysosin
What are the functions of the following proteins:
Troponin T
Troponin I
Troponin C
Troponin T - binds troponin to tropomyosin
Troponin I - inhibits the interaction of myosin with actin
Troponin C - contains the binding sites for Ca2+
What is the sarcoplasmic reticulum
Membranous sac that envelops the myofibrils. an AP results in Ca2+ channels opening in the SR which triggers contraction
What are the events that occur after the AP causes release of CA2+ from the SR
Ca2+ binds to Troponin C –> cross-linkages are formed between actin and myosin –> the thick and thin filaments slide past each other causing shortening
