Normal NMJ, Muscle Contraction, Myelination Flashcards
Describe AP generation
Describe the process of AP generation at the NMJ
Describe excitation contraction coupling
Describe how skeletal muscle is controlled from higher centers
RP = -70mV
Na enter => depolarisation
Depolarisation that exceeds threshold => VGNC open => +40mV
VGNC close, VGKC open
Repolarisation as K enters and hyperpolarises
VGKC close
RP restored by NaKATPase
Depolarisation reaches presynaptic membrane => VGCC opens => Ca influx
ACh exocytosed from vesicles
ACh binds to postsynaptic nicotinic receptor (LG) => cations enter
Many MEPPs summate to EPP => if threshold exceeded, AP generated along sarcolemma into T tubules
Depolarisation T tubules => Ca release from within SR stores
Ca binds to troponin => tropomyosin moves to reveal myosin binding sites with actin => muscle contraction
Cross bridges form
Brain => decussates in medullary pyramids lateral CST => interneuron => LMN in VH => muscle
Drugs that act at NMJ
Botulinum - prevents ACh release
-reduce muscle contraction
Curare - NAChR antagonist
-reduce muscle spasm in anaesthesia
Pyridostigmine - AChE inh => increase ACh in cleft (short term management of MG)
- MG - AI vs AChR => weakness, fatigue
- diagnosis made by measuring in plasma
Novichock - AChE inh => excess ACh in cleft
How does Cushings/Addisons relate to muscle function
ECC, NT are chemical events so can be affected by endogenous bioogical molecules
Cushings -excess cortisol release from adrenals -increased muscle protein catabolism -decreased muscle protein synthesis => muscle weakness/atrophy
Addisons
-decreased cortisol release from adrenals
-decreased appetite, fatigue
=> muscle weakness/atrophy
Describe the structure of muscle spindles/intrafusal muscles
Skeletal muscle fibre/extrafusal innervated by a motor
Spindles innervated by y motor
-contract if extrafusal contract
Spindle capsule => afferents via Group 1 fibres
- nuclear bag fibres - monitor dynamic changes in muscle length
- nuclear chain fibres - monitor static muscle length
Clinical uses of the stretch reflex
LMN lesions - hypo/areflexia (target muscles not making connections with spinal nerve
UMN - hyperreflexia (spinal nerve still in contact with target fibre but no UMN input, loss of descending inhibition
Stages of stretch reflex
Muscle spindle stretches
Afferent I => DRG => 2 pathways
Inh interneuron (Renshaw cell) => a motor => antagonistic muscle
a motor neuron => agonistic muscle and y motor neuron (spindle contraction)
Describe the 3 factors that contribute to signal decay in the axon
Describe the structure, importance and function of myelin
Membrane resistance (no of open ion channels)
-decreased no of open channels => less decay
Axial resistance (diameter)
-greater diamter => less decay
Membrane capacitance
-thicker membrane => smaller capacitance => less decay
Oligodendrocytes/Schwann cells wrap around the axon via many branches or 1 arm
Saltatory conduction via clusters of VGNC/pumps at Nodes of Ranvier where AP is regenerated
-fewer ion channels and pumps needed, making charge transfer more efficient in small sapces
Describe the process of myelinogenesis
Oligodendrocyte progenitors => oligodendrocytes via neuroglial signalling molecules/growth factors
Starts in 3rd trimester
Rapid increase from birth
-corresponds with motor and cognitive skills
Lifelong process
Examples of myelin related pathologies
- develpmental
- trauma
- degenerative/AI
Developmental - failure to myelinate/dysmyelination
Leukodystrophy
Cerebral Palsy
Myelin damage
- brain injury
- infection
- toxin
- ischemia/stroke
Neurodegenerative/AI
- MS
- GBS
- CPM
But demyelinated lesions increase with age
Symptoms of myelin loss
Failure of conduction of axons
-often slower, can stop
Impaired vision, hearing Tingling Weakness Cognitive disruption Memory loss Heat sensitivity Loss of dexterity, coordination, balance Difficulty controlling bowel movements,
