Overview of the Neurons, Neuronal Signaling, and Neural Networks (Part I)
Charcot-Marie-Tooth disease (MOA and S/Sx)
- AKA CMT -Loss of PNS axons leading to peripheral neuropathy -Signs & Symptoms •Motor dysfunction, sensory loss, muscle atrophy •Podiatry: Foot drop, high-stepped gait, hammertoe
Guillain-Barré (MOA and S/Sx)
-1-2 weeks following a viral infection -***Selectively attacks and damages PNS myelin (e.g. motor nerves)*** -Weakness is progressive and may require ventilatory assistance -Most get better over time but often with residual complications
Myasthenia Gravis (MOA)
-Autoimmune destruction of postjunctional nicotinic receptors -Decreases the availability of acetylcholine receptor sites
Lambert-Eaton Myasthenic Syndrome
-Ca2+ is blocked from entering presynaptic motor nerve terminals -Inhibits the release of acetylcholine
Tetrodotoxin (source and MOA)
-From Pufferfish -Concentrated in liver and ovaries of pufferfish -Prevents depolarization by preventing Na+ from entering
Anesthesia Considerations in MS
-Increase in body temperature can cause exacerbation -Increased seizure risk in these patients -Peripheral blocks, epidural, or spinal anesthesia? A) Epidural > Spinal, epidural is safer -Peripheral blockade has not been shown to exacerbate -Possible sensitivity with non-depolarizers A) Avoid succinylcholine (only depolarizing agent) -Consider steroid supplementation perioperatively
Multiple Sclerosis (MOA)
-Neuroinflammatory disease that impacts myelin -***Plaques occur due to an autoimmune attack of CNS myelin***
Tx for Multiple Sclerosis
-No cure, only symptom control/slowing progression -Corticosteroids -Interferon-B (beta) therapy -Immunosuppressants: e.g. Mitoxantrone (cardio toxic), Methotrexate
S/Sx of Multiple Sclerosis
-Optic nerve: visual disturbances -Cerebellum: gait disturbances -Spinal cord: Limb paresthesias, Limb weakness, Urinary incontinence, and Impotence
Curare
-Plant extract -Causes paralysis by binding to nicotinic receptors at NMJ -used with induction and surgery eventually
Botulism (MOA)
-Prevents presynaptic attachment and fusion of vesicles -Inhibits the release of acetylcholine
Multiple Sclerosis (Forms)
-Relapse-remitting: Exacerbations and remissions -Primary progressive: Slow continuous debilitation
Role of membrane proteins
-Serve as anchor points for cytoskeletal elements -Surface recognition molecules -Assist in movement of lipid insoluble nutrients (glucose) -Regulate the passage of ions into or out of the cell
What do Corticosteroids do in MS?
-Shortens duration of relapse -Accelerates recovery
Steps of Chemical Synaptic Transmission 5 steps
1) Synthesis of the neurotransmitter 2) Presynaptic concentration & packaging (e.g. vesicles) 3) Release into the synaptic cleft 4) Binding to receptors on postsynaptic membrane 5) Termination of neurotransmitter action
What is special about nodes of ranvier?
Contain high concentration of Na channels
Name two demyelinating diseases
Guillain-Barré Syndrome and Multiple Sclerosis
Treatment of choice for relapse-remitting MS?
Interferon-B (beta)
Fast synaptic receptors
Ionotropic receptors (ligan gated)
What three diseases interfere with neuromuscular transmission
Lambert-Eaton Myasthenic Syndrome Botulism Myasthenia Gravis
Slow synaptic receptors
Metabotropic receptors (g-protein)
Type of conduction from node to node along myelinated axons
Saltatory conduction
Relative Refactory Period (RRP)
This represents a time when a greater-than-normal stimulus may initiate an impulse.
Equilibrium potential of K+
Wants ot move out of cell (-94 mV)
Equilibrium potential of Na
Wants to more into cell (+60 mV)
Equilibrium potential of Ca2+
Wants to move into cell (+136 mV)
Equilibrium potential of Cl-
Wants to move into cell (-86mV)
What do we know about unmyelinated axons?
propagation is slow & continuous
Absolute Refractory Period
time during which another action potential is impossible; limits maximal firing rate
