BiM Neuromuscular Physiology

Question 1

1. What occurs in MND/ALS
2. Briefly describe features of early/intermediate/late stages of ALS
3. What occurs in MS
4. What are 3 types of MS

Answer 1

1. Progressive degeneration of upper and lower motor neurons - signals required for muscle movement are disrupted
2. Early - slight weakness in hands and limbs
   Intermediate - loss of motor control, fatigue, slurred speech
   Late - difficulty breathing, swallowing, paralysis
3. Demyelination of myelin sheath, affects conduction of electrical signals. Lesions form in CNS, auto-inflammatory response, myelin destroyed
4. Clinically isolated syndrome - first episode causes inflammation and damage
   Relapsing-remitting - symptoms worsen then improve predictably
   Secondary-progressive - more aggressive and progressive form of RRMS

Question 2

1. What are excitable cells
2. Name 2 groups of excitable cells
3. Describe the information flow through a neuron
4. What is the function of a glial cell
5. Name 3 types of glial cell and describe their function

Answer 2

1. Cells that are electrically. charged and use electrical currents to act
2. Nerve cells, muscle cells
3. Dendrites collect electrical signals. Cell body integrates incoming signal and generates outgoing signal. Axon passes signals to dendrites of another cell or to an effector cell
4. Support neurons
5. Astrocytes - regulate chemical content of extracellular space. Schwann cells - provide myelination of axons. Microglia - immune cells of CNS

Question 3

1. What types of axons take information from periphery to CNS
2. What types of axons convey information from CNS to muscles
3. Describe the function of the spinal cord roots
4. What are interneurons

Answer 3

1. Afferent/sensory axons
2. Efferent/motor axons
3. Dorsal root - contain afferent axons (send information to CNS)
   Ventral root - contain efferent axons (innervate muscles)
4. Neurons that connect sensory and motor neurons in the central nervous system

Question 4

1. Define resting membrane potential
2. What is the normal RMP
3. What equation is used to record RMP

Answer 4

1. Electrical charge (pd) across plasma membrane when cell is unexcited
2. -70mV
3. Nernst equation

Question 5

1. What is an action potential (AP)
2. Name 2 conditions in which APs may be disrupted
3. Describe the stages of AP generation and conduction
4. What is the refractory period
5. What are the phases of refractory period

Answer 5

1. Brief electrical pulse generated by bio electricity, fired by neurons when stimulated. Electrical signal that conveys information across nervous system (basic functional unit of nervous system)
2. MS, Charcot-Marie-Tooth syndrome, Alzheimer’s, ALS, locked-in syndrome
3. Hypopolarisation - voltage-gated Na channels closed. Stimulus changes membrane potential to threshold potential.
   Depolarisation (rising phase)- when threshold potential reached, voltage-gated Na channels open rapidly, causing influx of Na ions (cell becomes more electropositive), until equilibrium reached (overshoot)
   Repolarisation (falling phase) - voltage-gated Na channels close, reducing sodium permeability. Voltage-gated K channels open, causing efflux of K ions (cell becomes less electropositive)
   Hyperpolarisation (undershoot) - K ion efflux ‘overshoots’ reduction in electropositivity, and membrane potential is more negative than at rest, however this soon is re-established
4. Time after AP generation, during which the excitable cell cannot product another AP
5. Absolute - overlaps depolarisation and around 2/3 of depolarisation.
   Relative - period where AP generation is possible, but only with a supra threshold stimulus

Question 6

1. How are APs conducted along unmyelinated axons
2. List 3 factors influencing conduction velocity
3. What is the definition of saltatory conduction
4. Describe saltatory conduction

Answer 6

1. Na channels open in response to stimuli, generating AP.
   Some depolarising current passively flows down axon.
   Local depolarisation causes neighbouring Na channels to open, generating further APs
   Upstream Na channels close, causing K channels to open
   Membrane potential depolarises and axons become refractory
2. Plasma membrane resistance, cytoplasm resistance/axon diameter, Na channel density
3. Method by which nerve impulses move down myelinated axons
4. APs initiate at axon initial segment
   Propagation along axon
   Excitation only occurs at Nodes of Ranvier (space between sheaths)
   Depolarisation occurs, opening Na channels at node.
   Passive depolarisation to next node, opens Na channel on second node (domino effect)
   Conduction is much quicker

Question 7

1. Describe the function of A-a, A-b, A-d and C-fibres
2. Define dermatome
3. What encodes the strength and duration of a stimulus
4. What encodes the onset/offset of a stimulus

Answer 7

1. A-alpha - proprioception (skeletal muscle)
   A-beta - mechanoreceptors
   A-delta - pain, temperature
   C-fibres - pain, temperature, itch
2. Area of skin that contains primary afferents that transduce information from periphery to spinal cord
3. AP firing frequency
4. Timing of first/last AP

Question 8

1. How do neurons communicate with each other
2. Where does this communication occur
3. What are neurotransmitters. Give 3 classes of NTs
4. How are NTs synthesised and stored

Answer 8

1. Chemical neurotransmission
2. Synapses
3. Signalling molecule secreted by a neuron to affect another cell across a synapse.
   Amino acids (GABA), monoamines (dopamine, noradrenaline, adrenaline, serotonin, histamine), peptides, others (acetylcholine)
4. Enzyme synthesised in cell body is slowly transported through axon. Enzyme synthesises and packages NT. NT released and diffuses, leading to transport of precursors into terminal

Question 9

1. How is NT release initiated
2. Describe the exocytosis/endocytosis cycle in relation to NTs

Answer 9

1. AP invades presynaptic terminal, causing membrane depolarisation.
   Voltage-gated Ca ion channels open. Increase in calcium promotes vesicle fusion (with membrane - exocytosis). Vesicles release NTs into synaptic cleft
2. Docking - vesicle binds to membrane, before AP invades terminal
   Ca ion sensing - Ca ion entry triggers vesicle fusion
   Endocytosis - new vesicle membrane punched off
   Loading - new vesicle filled with neurotransmitter

Question 10

1. What branch of the nervous system controls skeletal muscle
2. What branch of the nervous system controls smooth/cardiac muscle and gland cells
3. Briefly describe what NTs are involved in the sympathetic NS
4. Briefly describe what NTs are involved in the parasympathetic NS

Answer 10

1. Somatic nervous system
2. Autonomic nervous system
3. Fight/flight/fright.
   Chain of sympathetic ganglia - preganglionic neurons release ACh and postganglionic neurons release NA. NA binds to various adrenreceptors, causing bronchodilator, raising HR, increasing PR, dilating pupils
4. ACh released, binding to different post-synaptic ACh receptors, causing rest-and-digest response

Question 11

1. Where are lower motor neurons found
2. What does one lower motor neuron do
3. Neurons innervating axial muscles are found where in relation to those innervating distal muscles
4. Neurons innervating flexors are found where in relation to those innervating extensors

Answer 11

1. Ventral horn of spinal cord
2. Innervate a single muscle
3. Medial within ventral horn
4. Dorsal in ventral horn

Question 12

1. What is a motor unit
2. What is a motor neuron pool and what is the advantage of a motor neuron pool

Answer 12

1. Alpha motor neuron and all the muscle fibres it innervates. Alpha motor neurons directly trigger generation of force by muscles
2. Collection of alpha motor neurons that innervate a single muscle. Arrangement maintains normal muscle activity when damage to single motor neuron occurs

Question 13

1. What is the neuromuscular junction (NMJ)
2. What are the 3 components of the NMJ
3. What happens when NT is released at the NMJ
4. What is a sarcolemma
5. What is the function of a myofibril
6. What is the sarcoplasmic reticulum
7. What is the motor endplate

Answer 13

1. Synapse between terminal end of a motor nerve and a muscle. Site of AP transmission between nerve and muscle
2. Presynaptic terminal, synaptic cleft, postsynaptic membrane (of skeletal muscle fibre)
3. Muscle contraction
4. Excitable cell membrane covering muscle fibre
5. Contract in response to an AP sweeping down sarcolemma
6. Extensive intracellular sac that stores Ca ions
7. Postsynaptic membrane that faces axon terminal and contains many folds containing nicotinic receptors

Question 14

1. Briefly describe neural transmission in the sympathetic nervous system
2. Briefly describe neural transmission in the parasympathetic nervous system

Answer 14

1. Efferent signals carried from CNS via two neurons.
   Preganglionic neurons release ACh at the autonomic ganglia, which activates nicotinic receptors on postganglionic neurons. This leads to release of NA, which activates adrenergic receptors in peripheral target tissues
2. Efferent signals carried from CNS via two neurons.
   Preganglionic neurons release ACh at the autonomic ganglia, which activates nicotinic receptors on postganglionic neurons. This leads to release of ACh, which activates muscarinic receptors in peripheral target tissues

Question 15

1. Define reflex
2. Give 3 examples of a reflex

Answer 15

1. Involuntary, nearly instantaneous movement in response to a stimulus
2. Myotatic/stretch reflex, patellar/knee-jerk reflex, crossed-extensor reflex, vestibulo-occular reflex

Question 16

1. What is an autonomic ganglion
2. Where do sympathetic pathways originate in the spinal cord
3. Where do parasympathetic pathways originate in the spinal cord
4. Where are sympathetic ganglia found
5. Where are parasympathetic ganglia found

Answer 16

1. Where two neurons (preganglionic and postganglionic) synapse
2. Thoracic and lumbar regions
3. Brainstem (leave vial cranial nerves) and sacral region
4. Close to spinal cord (short preganglionic, long postganglionic neurons)
5. Close to/on taget organs (long preganglionic, short postganglionic neurons)

Question 17

1. Where do most postganglionic neurons secrete NA onto
2. Where do most postganglionic neurons secrete ACh onto
3. What enzyme removes/breaks down NA from the synapse
4. What enzyme removes/breaks down ACh from the synapse
5. What is NA synthesised from
6. What is ACh synthesised from
7. What is the name of the structure of the region from which NTs are released in sympathetic and parasympathetic branches

8 What breaks down ACh

Answer 17

1. Adrenergic receptors
2. Muscarinic/nicotinic receptors
3. Monoamine oxidase (MAO)
4. Achesterase (AChE)
5. Tyrosine
6. Acetyl CoA and choline
7. SyNS - varicosities
   PSyNS - varicosities and axon terminals
8. AChE

Question 18

1. List 5 features which occur after activation of the sympathetic NS
2. What does the adrenal medulla secrete
3. What are chromaffin cells and what do they do

Answer 18

1. Pupils dilate, eyelids open, sweat glands stimulated, BV dilation in large muscles, increase HR, increase contractility, bronchodilation, increase PR, inhibit salivary glands (dry mouth)
2. Hormones and adrenaline
3. Axonless cell bodies that secrete adrenaline directly into bloodstream

Question 19

1. What are muscarinic receptors and where are they found
2. List 5 features which occur after activation of the parasympathetic NS

Answer 19

1. ACh receptors that form G protein-coupled receptor complexes. Five subtypes
   M1 - autonomic ganglia, salivary glands, stomach, CNS
   M2 - cardiac muscle, CNS
   M3 - salivary glands, stomach, CNS
   M4 - CNS
   M5 - CNS
2. Pupils constrict, eyelids narrow, sweat glands inhibited, BV constriction in large muscles, decrease HR, decrease contractility, bronchoconstriction, decrease PR, activate salivary glands, stimulate stomach secretions and intestine activity, stimulate lung secretions

Question 20

1. What do neural agonists do. Give 2 examples
2. What do neural antagonists do. Give 2 examples
3. What do indirect agonists do. Give 2 examples

Answer 20

1. Bind to receptor and mimic action of endogenous ligand. Salbutamol, atenolol
2. Bind to receptor and block NT action. Propranolol, atropine
3. Affect secretion/uptake or degradation of NT. Cocaine, SSRIs, MAOIs

Question 21

1. How many neurons are involved in somatic motor control
2. Where do SNS neuron cell bodies reside
3. What is the function of collagen fibres in the synaptic cleft
4. Define and describe the process of excitation-contraction coupling

Answer 21

1. Single neuron originates in CNS and projects to target tissue
2. Brain or ventral horn of spinal cord
3. Hold axon terminal and motor endplate in alignment
4. Rapid communication between electrical events occurring in the plasma membrane of skeletal muscle fibres and Ca ion release from SR, leading to contraction

AP arrives in alpha motor neuron causing ACh exocytosis (release into synaptic cleft from axon terminals). ACh binds to nicotinic receptors in motor endplate, causing postsynaptic depolarisation and voltage-gated Na channels to open (Na ion influx).
This creates end-plate potential and when EPP reaches threshold, muscle AP is initiated.
AP conducted across surface of muscle fibre into T-tubules, binding to DHP receptors (voltage-gated L-type Ca channels). This causes Ca ions to be released from SR into the cell down concentration gradient into sarcoplasm
This Ca acts on regulatory proteins (troponin C), causing a conformational change, and troponin dissociates from actin/tropomyosin complex, exposing myosin binding sites on actin. Myosin binds ATP, dissociates from actin, pivots and rebinds actin (cross bridge). This sliding/shortening actin/myosin filaments (sarcomere) causes contraction.
When Ca ion concentration is reduced, troponin and tropomyosin prevent actin/myosin cross bridge formation. Relaxation occurs due to reduction in Ca ion (or ATP) levels

Question 22

1. Define fascicle
2. What are myofibrils composed of
3. What is myosin
4. Outline the structure of myosin
5. What 2 molecules bind to myosin

Answer 22

1. Group of adjacent fibres bundled together in units, with collagen, nerves, BVs and elastic fibres found in between
2. Actin, myosin, tropomyosin, troponin, titin, nebulan
3. Motor protein of myofibril
4. Intertwined protein chains that form long filament with pair of bulbous heads
5. Actin, ATP

Question 23

1. What is actin
2. What 2 forms can actin take
3. What is a sarcomere
4. What are the 5 characteristic features in a sarcomere
5. What is the function of titin
6. What is the function of nebulin
7. What is the role of troponin
8. What is the role of tropomyosin

Answer 23

1. Protein that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils
2. G-actin - globular
   F-actin - part of a linear polymer microfilament
3. Basic contractile unit of a myocyte (muscle fibre) - one repeating pattern of thick (myosin) and thin (actin) filament
4. Z-discs - proteins that allow thick filaments to attach to each other
   I-bands - region occupied by thin filaments
   A-band - contains thick and thin filaments. Centre of sarcomere spanning H-zone
   H-zone - region occupied by thick filaments
   M-line - centre of sarcomere, through
5. Provides elasticity and stabilises myosin
6. Aligns actin filaments
7. Controls position of tropomyosin
8. Wraps around actin filament, partially blocking myosin binding site

Question 24

1. What is muscle power stroke
2. Describe how ATP provides energy for power stroke
3. Describe power stroke process
4. Why does rigor mortis occur

Answer 24

1. Key force-generating step used by myosin motor proteins. Forces are generated on the actin filament as the myosin protein reverts back to its original conformation
2. ATP binds to myosin head, and myosin acts as ATPase, releasing phosphate group and energy. Released energy is trapped and stored as potential energy, which fuels the powerestroke that moves actin
3. ATP binds to myosin, which dissociates from actin. Myosin head swings over and binds weakly to new actin. Myosin head rotates on hinge, pushing actin filament past. Myosin head releases ADP and resumes tightly bound rigorous state
4. After death, ATP generation stops and muscles stiffen as cross bridges do not move

Question 25

1. What is muscle fatigue
2. What are 3 classifications of muscle
3. Give 3 differences between each muscle type

Answer 25

1. Condition whereby muscle is no longer able to generate or sustain expected power output
2. Slow-twitch (type I)
   Fast-twitch oxidative-glycolytic (type IIa) - FOG
   Fast-twitch glycolytic (type IIb) - FG
3. ST - slow development of tension, small diameter, long contraction duration, fatigue resistant, aerobic respiration, high capillary density, many mitochondria
   FOG - intermediate development of tension, medium diameter, short contraction duration, fatigue resistant, glycolytic respiration, medium capillary density, moderate mitochondria
   FG - fast development of tension, large diameter, short contraction duration, fatigue quickly, glycolytic respiration, low capillary density, few mitochondria

Question 26

1. What is a muscle motor unit
2. What motor unit is likely to contain more muscle fibres - one for fine motor skills or gross motor actions
3. What is contraction summation
4. What type of muscle contraction is caused by summation

Answer 26

1. Basic unit of contraction - group of muscle fibres that function together and somatic motor neuron that controls them
2. Gross motor actions
3. Generation/propagation of multiple stimuli, without time for muscle to relax fully (stimuli closer together) - when repeated muscle twitches occur before the previous twitch has fully relaxed
4. Tetanus