Action Potentials and Channelopathies

Question 1

Structure of Neurons

Answer 1

• Soma (cell body)
  
  • machinery to maintain cell
• Dendrites
  
  • short
  • transport impulse towards cell body
  • many types of ligand-gated channels
  • voltage-gated Ca²⁺ channels
• Axons
  
  • longer
  • transport impuses away from cell body
  • primarily voltage-gated Na⁺ channels at nodes of Ranvier

Question 2

Nernst equation

Answer 2

Membrane potential at equilibrium.

concentration gradient = electrical gradient

net current equals zero ⇒ reverse potential

E_x = RT/zF x ln [X]o / [X]i

E_k = -94 mV

E_Na = + 60 mV

E_Cl = -86 mV

E_Ca = +136 mV

Question 3

Receptors

Answer 3

• Detects specific stimulus
• Use stimulus gated ion channels to produce a receptor potential
  
  • Ohm’s law (V=IR) ⇒ current x membrane resistance = voltag change
• Intensity/duration of stimulus ⇒ size/duration of recpetor potential
  
  • Graded response
• Time constant (t = RC)
  
  • Time before reeptor reaches final amplitude
    
    • influences whether or not signal arriving in a similiar time frame reinforce each other ⇒ temporal summation
• Distance signal travels depends on:
  
  • capacitance
  • membrane resistance
  • length constant

Question 4

Action Potential

Answer 4

1. Small depolarization of axonal membrane
2. Opening of voltage-gated Na channels in resting state
   
   • m gates open, h gates begin to close
3. Na flows into cell ⇒ further depolarization ⇒ threshold
4. Positive feed-foward loop (Hodgkins cycle) ⇒ E_Na
5. Na channels inactivated (h gates closed) and voltage gated K channels open (n gate)
6. Membrane repolarizes
7. K open, Na closed ⇒ hyperpolarization
8. K channels close ⇒ resting potential

Question 5

Post-synaptic Responses

Answer 5

• Excitatory synapses
  
  • Usually involves Na and K channels allowing Na to enter cell
  • Causes membrane depolarization ⇒ excitatory post-synaptic potential (EPSP)
  • Moves membrane closer to threshold
  • Increased possibility of firing AP
• Inhibitory synapses
  
  • Usually involves Cl channels allowing Cl to enter cell
  • Causes membrane hyperpolarization ⇒ inhibitory post-synaptic potential (IPSP)
  • Moves membrane away to threshold
  • Decreases possibility of firing AP
• Overall post-synaptic potential is the sum of EPSPS/IPSP due to temporal or spatial summation.

Question 6

Tetrodotoxin

Answer 6

• Found in Japases puffer fish
• Blocks Na⁺ channels preventing AP

Question 7

Conotoxin

Answer 7

• Found in snails, spiders, and snakes
• Binds to Ca²⁺ channels

Question 8

Bungarotoxin

Answer 8

Binds to ACh Receptors.

Question 9

Tetanus and Bolulinum Toxin

Answer 9

Binds to specific parts of the secretory protein machinery at presynaptic membrane.

Question 10

Curare

Answer 10

Affects the receptors of neurotransmitters.

Binds nicotinic receptors and prevents them from opening blocking transmission.

Question 11

Latrotoxin

Answer 11

Black widow spider venom.

Leads to massive influx of calicum causing depletion of synaptic vesicles.

Question 12

Hyperkalemic Periodic Paralysis

(HYPP)

Answer 12

• Caused by mutation of voltage gated Na⁺ channel
• Triggered by exertion and increase in extracellular potassium
• Abnormal Na⁺ channels do not inactivate fully after depolarization
  
  • Constant Na⁺current and slight depolarization
  • Unable to fire action potential
  • Muscle fibers inexcitable for minutes to hours

Question 13

Hypokalemic Periodic Paralysis

(HOPP)

Answer 13

• Mutated voltage gated Ca²⁺ channel with enhanced inactivation
• Autosomal dominant
• Low resting potentials
• Action potentials with little overshoot
• Episodes of muscle weekness

Question 14

Myotonia

Answer 14

• Mutation of Cl^- channel with increased resistance to flow
  
  • Cl permeability decreases
  • Time contant increases
• Resting membrane potential becomes more K dominated
• Small changes in extracellular K cause more depolarization
• Stimulus which would normally cause 1 AP causes many
• Muscles take unusually long time to relax following contraction

Question 15

Multiple Sclerosis

Answer 15

• Progressive demyelination of CNS neurons
  
  • Loss of AP conduction
  • Plaques form on demyelinated white matter
  • Plasticity causes increased Na channels of a different type sites of demyelination
• Diagnosed with MRI, CSF analysis, or evoked potentials
• Treat with neuroprotective interventions to maintain axonal integrity
• Symptoms
  
  • muscle weakness
  • hypoesthesias
  • nystagmus and diplopia
  • ataxia
  • dysarthria
  • dysphagia
  • cognitive impairment and emotional symptoms

Question 16

Guillain-Barre Syndrome

Answer 16

• Rapid progressive ascending paralysis
• Due to immune response causing macrophages to selectively attack PNS myelin
• Usually follows ~ 1 week after viral infection
• Motor nerves mostly affected
• Symptoms:
  
  • rapid development of muscle paralysis
  • areflexia
  • no fever

Question 17

Myasthenia Gravis

Answer 17

• Autoimmune destruction of nicotinic ACh receptors at NMJ
  
  • Decreased transmission at NMJ
  • Amplitude of compound APs measured with surface electrodes decreases rapidly
• Weakness especially likely to affect cranial muscles & limbs
  
  • Improved after exercise
  • Severity varies throughout the day, day to day, and over periods
• Junctional folds sparse or shallow
• Wide synaptic clefts
• Treat with AchE such as edrophonium

Question 18

Lambert-Eaton Syndrome

Answer 18

• Auto-antibodies against Ca²⁺ channel in the nerve ending of NMJ
  
  • Decreases normal Ca influx
  • Decreased exocytosis and transmitter release
  • Smaller end plate potential
  • Weakness of muscle contraction
• Repetitive stimulation results in incrementing responses