neurons Flashcards

1
Q

describe the cell membrane of neuron

A
  • composed of phospholipid bilayer
    • isolates cell cytosol from extracellular fluid
  • impermeable
  • 3-7nm

Phospholipid structure ;

  • Polar hydrophilic head
  • Phosphate group
  • Non polar hydrophobic double hydrocarbon tail
  • Water cannot cross hydrophobic domain
    • Cannot leave or enter cell
    • Ions dissolved on either side cannot either
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2
Q

how do ion channels control flow of ions across the phospholipid bilayer

A
  • closed ion channels are impermeable to H2O and dissolved ions
  • binding of ligands (neurotransmitters) or changes in voltage across the bilayer can open ion channels
    • change of conformation
  • open ion channels allow passage of ions across the lipid bilayer
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3
Q

how does electrochemical gradient effect flow of ions through an open ion channel?

A

individual ions diffuse from areas of high concentration to low

  • until reach same concentration on both sides
  • rate of diffusion depends on temperature
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4
Q

how does electrochemical forces effect flow of ions through an open ion channel?

A

partially determines flow of ions

  • ions with like charges repel each other
  • ions with opposite charges attract
  • therefore gradient will not fully equalise
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5
Q

what is the role of the Na+/K+ pump in the cell membrane?

what is this pump powered by?

A

pumps K+ ions into neurons

pumps Na+ out of neurons

  • extracellular fluid contains10-fold higher concentration of Na+ ions than neuronal cytoplasm
  • powered by ATP hydrolysis
    • energy dependent
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6
Q

what is an equilibrium potential?

A

The equilibrium potential of an ion is the electrical potential difference across the cell membrane that exactly balances the concentration gradient for that ion (assuming the membrane is permeable to only that ion)

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7
Q

what is resting potential?

A

The differential permeability of Na+ and K+ voltage-gated ion channels in resting neurons generates the resting potential

due to Na+/K+ pump:

  • 20x more K+ inside neurons than ouside
  • 10x more Na+ outside neurons than inside
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8
Q

how is resting potential established?

A

In resting neurons

  • Voltage-gated K+ channels are relatively permeable to K+ ions passing through them
  • K+ ions can also leave the cytosol through the membrane spanning K+/Cl- co-transporters;
    • KCC2, 3 or 4

Therefore

  • K+ ions diffuse out of the neuron down their concentration gradient until equilibrium
  • Influx of Na+ ions through Na+ channels is minimal

The result

  • Inside of neuron plasma membrane becomes negatively charged compared to the outside (-65mV)
  • Resting membrane potential of neuron = -65mV
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9
Q

how is neuronal excitability and function regulated?

A

ion and ion channels play role in regulation of neuronal excitability and function

calcium ions

chloride ions

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10
Q

how do calcium ions have a role in regulation of neuronal excitability?

A
  • Ca2+ present at 10,000x higher conc outside neurons than inside
    • A transmembrane ATPase/Ca2+ pump removes Ca2+ from neurons
    • Intracellular Ca2+ binding proteins sequester free Ca2+
    • Intracellular Ca2+ stores reduce cytosolic calcium levels even further
  • leads to opening of voltage or ligand gated Ca2+ channels lead to
    • Ca2+ influx
    • depolarisation
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11
Q

how do chloride ions have a role in regulation of neuronal excitability?

A
  • Cl- ions are present at an 11.5-fold higher concentration in the extracellular fluid compared to the neuronal cytosol
    • Cl- ions are co-transported out of neurons along with K+ ions by the potassium/chloride co-transporter proteins,
      • KCC2, KCC3 and KCC4 (KCC2 is CNS specific)
  • Leads to the opening of ligand-gated Cl- channels leads to
    • Cl- influx
    • hyperpolarization of neurons (more negative membrane potential)
      • less likely to have action potential
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12
Q

what occurs in the rising phase of an action potential?

A

initiation of depolarisation

  • local depolarisation - due to Na+/Ca2+ influx
    • Opening of neurotransmitter gated ion channels at post-synaptic membrane
    • Direct activation of nociceptor terminals by heat, cold, noxious chemicals etc.

threshold

  • If depolarisation reaches a critical threshold
    • Rapid opening of voltage-gated Na+ channels
    • Massive influx of Na+ ions into neurons
      • Driven by a large electrochemical gradient
    • Rapid increase in membrane potential
      • Overshoots neutral
      • Membrane potential transiently +30 to +40 mV
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13
Q

what occurs in the falling phase of an action potential?

A

at apex of overshoot

  • Voltage-gated Na+ channels close
  • Voltage gated Ka+ channels fully open
  • More than at resting potential

->

  • Inward Na+ current stopped
  • Outward K+ current initiated
  • Rapid repolarisation
  • The falling phase is followed by an undershoot or period of hyperpolarisation
  • Hyperpolarisation is followed by a gradual restoration of the membrane potential to resting potential
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14
Q

how do ion channels change in the duration of an action potential?

A

at threshold

  • Voltage-gated Na+ channels open extremely rapidly
  • Voltage-gated K+ channels are also stimulated to open fully (slowly open)
    • slow kinetics of voltage-gated K+ channels means opening is delayed by almost 1 msec
  • Voltage-gated Na+ channels rapidly and spontaneously close about 1 msec after opening

at overshoot

  • Na+ channels close and K+ channels open
    • repolarisation
  • Voltage-gated K+ channels are stimulated to close back to baseline permeability levels by repolarization of the plasma membrane back to threshold potential
  • slow kinetics of voltage-gated K+ channel closing leads to the hyperpolarized undershoot
  • Inwardly rectifying K+ channels return the membrane potential to resting potential after hyperpolarization
  • Voltage-gated Na+ channels cannot open again until the plasma membrane has been hyperpolarized
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15
Q

describe action potential conduction along non-myelinated axons

A
  • Na+ influx through volatage channels during rising phase
  • Na+ diffuses laterally in juxta-membrane cytosol
    • leads to depolarisation of plasma membrane infront of rising AP
  • this depolarisation meets cluster of voltage gated Na+ channels
    • triggers seconds AP
  • repeated - AP propagated along axon
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16
Q

why can an action potential not go backwards?

A

requires hyperpolarisation

  • Voltage-gated Na+ channels in the membrane behind the AP need to be re-primed
    • ​​membrane potential must drop below threshold potential before they can reopen
17
Q

describe action potential conduction along myelinated axons

A

saltatory conduction

  • Nodes of Ranvier contain high concentrations of Na+ and K+ voltage-gated ion channels
    • Very few Na+ and K+ channels under the myelin sheath
  • Action potentials fire and Na+ floods into the axon at nodes
  • Na+ current flows quickly along the inside of the axon as myelin prevents current leakage
  • Voltage-gated Na+ channels at the next node are triggered to open by the depolarizing internal
18
Q

what effect nerve fibre conduction velocity?

A

conduction velocity proportional to

  • Nerve fibre diameter
  • Myelination thickness
19
Q

what are the groups of nerve fibres

give details about their

  • myelination
  • thickness
  • speed
A

myelination thickness speed

Aα fibre +++ +++ +++

Aβ fibre ++ ++ ++

Aδ fibre + + +

c-fibre x x +

20
Q

what occurs at the synapse?

A
  • axon terminal contain many mitochondria - provides energy for neurotransmitter release
  • synaptic bouton -
    • filled with vesicles of neurotransmitter
    • many proteins which regulate synaptic vesicle docking and exocytosis
  • main depolarising ion channel in synapse = voltage gated Ca2+ channels
  • AP reaches syanpse - voltage gated Ca2+ channels open - influx
  • Ca2+ entry - synaptic vesicle exocytosis and release of neurotransmitter into synaptic cleft
  • Postsynaptic neurotransmitter-gated ion channels either
    • depolarize post synaptic neurons (excitatory neurotransmitters) or
    • hyperpolarize them (inhibitory neurotransmitters)
21
Q

what are the two types of neurotransmitter receptors?

A

ionotropic neurotransmitter receptors

metabotropic neurotransmitter receptors

22
Q

what are ionotropic neurotransmitter receoptors?

A

ligand gated ion channels

  • activation by ligand binding
    • ion pore opens
  • rapid, short lived effects
  • examples :
    • Ligand-gated sodium channels (eg. nAChR)
    • Ligand-gated cation channels (eg. NMDAR)
    • Ligand-gated chloride channels (eg. GABA-A receptor)
23
Q

what are metabotropic neurotransmitter receoptors?

A
  • activation initiates intracellular signalling cascade
    • ions do not pass through receptor protein
    • signalling can alter gene expression, protein function and modulate ion channel gating
  • they are often GPCRs
  • slow acting and long lasting effects
  • examples :
    • Metabotropic glutamate receptors (mGluRs)
    • Adrenergic receptors of the autonomic nervous system (e.g. beta-adrenergic receptors in heart)