Synapses and ion channels Flashcards

1
Q

What is current across the plasma membrane?

A

Current = Net flux = Influx - Efflux

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2
Q

How is passive flux produced?

A
  • Ions: Electrochemical gradient

- Uncharged particles: Chemical gradient

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3
Q

Why is there flux at rest?

A

Because the resting potential is not equal to the equilibrium potential for any ions.

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4
Q

What are the ways that substances can cross the plasma membrane?

A
  1. Diffusion across PM directly.
  2. Diffusion through pores that are always open.
  3. Diffusion through channels that can open/close.
  4. Transport by carriers.
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5
Q

What are the types of primary active transporters (ATPases)?

A
  1. F-type: E.g. ATP synthase.
  2. V-type: E.g. Transports H+ into vesicles.
  3. P-type: E.g. Na+/K+-ATPase.
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6
Q

What is the importance of the electrogenic nature of Na+/K+-ATPase?

A
  1. Negative feedback: The more a cell is stimulated, the higher the internal [Na+], the greater the activity of the ATPase. This hyperpolarises cell and makes it harder to stimulate. Prevents depletion of ionic gradients.
  2. Contributes to resting potential.
  3. Allowed us to elucidate the molecular mechanism of the pump.
  4. May play role in pattern of APs.
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7
Q

What is the other important function of Na+/K+-ATPase?

A

Maintains osmotic pressure.

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8
Q

Which pumps maintain Ca2+ concentration gradient?

A
  1. NCX (Na+/Ca2+ exchanger)

2. PMCA (Plasma Membrane Ca2+ ATPase)

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9
Q

What is the mechanism of action for NCXs and PMCAs?

A
  • NCX: Pumps 3Na+ ions into the cell for every Ca2+ pumped out of the cell. It is electrogenic.
  • PMCA: Pumps 1 Ca2+ ion out of the cell for every 2 H+ ions pumped into the cell.
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10
Q

What are the types of secondary active transporters?

A
  1. ATP-Binding Cassette (ABC) Transporters: E.g. CFTR.

2. Solute Carrier (SLC) superfamily transporters: Main type of secondary active transporter in body.

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11
Q

What are cotransporters (symporters)?

A

All solutes travel in the same direction.

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12
Q

What are the important cotransporters?

A
  • NBC transporter: Pumps 3 HCO3- ions out of the cell along with 1 Na+.
  • NKCC transporter: Transports 1Na+:1K+:2Cl- ions out of the cell.
  • SGLT transporter: Transports glucose and Na+ ions out of cell (SGLT2- 1Na+:1Glucose, SGLT1: 2Na+:1Glucose).
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13
Q

What are exchangers (antiporters)?

A

Solutes travel in different directions across the PM.

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14
Q

What are important exchangers?

A
  • NHE: Pumps 1 H+ out for every Na+ in.
  • HCO3-/Cl- exchanger: Pumps 1 H+ and 1 Cl- out of cell for every Na+ and HCO3- pumped into cell.
  • Na+-dependent glutamate transporter: Pumps 1 H+, 3 Na+ and 1 Glu- ion into cell for every K+ pumped out of cell.
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15
Q

What are the roles of glial cells?

A
  1. Supports neurone
  2. Produces myelin
  3. Removes debris from injured cells
  4. Take up neurotransmitters
  5. Guides axons in development
  6. Regulates synaptic properties
  7. Forms BBB.
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16
Q

What is the importance of transporters?

A

Because there’s flux of all ions across the plasma membrane, this would deplete ionic concentration gradients needed for other cellular functions. Transporters maintain constant concentration gradients of ions.

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17
Q

Which channel is more important in cellular Ca2+ homeostasis?

A
  • NCX is more important in synapses, but not cell bodies.

- PMCA simply creates steeper gradient.

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18
Q

What is a synapse?

A

Functional connection between 2 nerve cells, 2 electrically excitable cells or a nerve cell and an effector cell.

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19
Q

What are the common locations of electrical synapses in mammals?

A
  • Smooth muscles
  • Cardiac muscles
  • Motorneurone controlling eye movement
  • Retinal photoreceptors
  • Astrocytes
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20
Q

What is the structure of electrical synapses?

A

Plasma membranes of both excitable cells connected at gap junctions by connexon channels.

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21
Q

What are the differences between chemical and electrical synapses?

A
  • Direction: Electrical synapses are usually 2-way whereas chemical synapses are always 1-way.
  • Speed: Chemical synapses are slower than electrical synapses (by ~0.2 ms).
  • Inhibition: Inhibition can only happen with chemical synapses (via IPSPs), but not electrical synapses.
  • Facilitation/modulation: Changes in structure of synapses and connections only possible for chemical synapses (important in learning).
  • Amplification: Only possible with chemical synapses.
  • Synchronisation: Only possible with electrical synapses.
22
Q

What is the significance of amplification at chemical synapses?

A
  • Small amount of energy at pre-synaptic terminal allows release of NTs that cause many ion channels to open on post-synaptic membrane, causing large amount of energy stored by polarised plasma membrane to be released.
  • This allows small cells (e.g. motor neurones) to stimulate much larger cells (e.g. muscle cells).
23
Q

What is an integrative synapse?

A

Stimulation of the pre-synaptic terminal causes NT release that does not necessarily depolarise post-synaptic terminal to above threshold. Instead, multiple pre-synaptic terminals may need to be activated.

24
Q

What is a relay synapse?

A

Stimulation of the pre-synaptic terminal causes release of NT that will always depolarise post-synaptic terminal to above threshold and cause AP?

25
Q

What is convergence and divergence?

A
  • Convergence: When multiple pre-synaptic neurones synapse with 1 post-synaptic neurone.
  • Divergence: When 1 pre-synaptic neurone synapses with multiple post-synaptic neurones.
26
Q

What is the sequence of events in a knee-jerk reflex?

A
  1. Stretch receptors in the muscle activated, stimulating AP which travels up the sensory neurones towards the CNS.
  2. In the spinal cord, the sensory neurones diverge and synapse with multiple motor neurones in a ‘motor neurone pool’.
  3. Sensory neurones stimulate motor neurones in motor neurone pool and causes APs that propagate down the motor neurones.
  4. APs in motor neurones cause release of ACh at neuromuscular junctions, creating EPPs that cause contraction of the quadriceps muscles.
27
Q

What are Renshaw cells?

A

Inhibitory interneurones that carry out feedback inhibition of motor neurones to prevent excess excitation. They are stimulated by recurrent collateral branches of motor neurones.

28
Q

What are EPSPs?

A
  • Excitation of pre-synaptic terminal causes release of NTs that lead to depolarisation of the post-synaptic terminal.
  • They increase the chance of APs occurring in post-synaptic terminal.
29
Q

What are IPSPs?

A
  • Excitation of pre-synaptic terminal causes release of NTs that lead to hyperpolarisation of the post-synaptic terminal.
  • They decrease the chance of APs occurring in post-synaptic terminal.
30
Q

What evidence is there to suggest that vesicles are responsible for NT release?

A
  1. MEPPs measured by Katz et al.
  2. Vesicle can clearly be seen at the pre-synaptic terminal by EM.
  3. Rapid freezing can be used to observe exocytosis of vesicles.
  4. Total neurotransmitter proportional to number of vesicles.
  5. Secretion of NT increases area of pre-synaptic membrane.
  6. Dye in vesicles released when pre-synaptic terminal stimulated.
31
Q

What is the advantage of NT in vesicles?

A

Maximises rate of NT release.

32
Q

How are vesicles filled?

A
  1. Vesicle synthesised in the cell body from ER and then Golgi body.
  2. Vesicles are transported to the pre-synaptic terminal down axon along microtubule network.
  3. V-type H+-ATPase loads H+ ions into the vesicle by active transport.
  4. Co-transporters use energy from efflux of H+ down electrochemical gradient to load vesicles with NTs.
33
Q

How are NTs re-uptaken?

A
  • Some are broken down (e.g. ACh by AChE) and re-uptaken as raw components.
  • Some are re-uptaken through transporters.
34
Q

What is responsible for EPSPs?

A

Bi-ionic channels permeable to both Na+ and K+.

35
Q

What is responsible for IPSPs?

A
  • K+ channels

- Cl- channels

36
Q

What is the reverse potential for EPSPs and EPPs?

A

Around half way between E_Na and E_K.

37
Q

How can inhibition be achieved?

A
  • Feedforward: Inhibitory signals are sent to the effector simultaneously with the excitatory signals. Prevents stimulation by weak stimuli.
  • Feedback: Inhibitory signals inhibit motor neurones and prevents over-stimulation.
38
Q

How do IPSPs work?

A

IPSPs don’t necessarily work by hyperpolarisation. Instead, they increase the outward current and thus reduce the net inward depolarising current from the EPSPs.

39
Q

What criteria are used to identify neurotransmitters?

A
  1. Must mimic action of natural NT when applied to post-synaptic terminal.
  2. Must be released from pre-synaptic terminal.
  3. Action must be blocked by same inhibitors as natural neurotransmitter.
  4. Enzymes must be present in pre-synaptic neurone to synthesise it.
40
Q

What neurotransmitter and receptor are present for somatic nerve synapses (NMJ)?

A
  • NT: ACh

- Receptor: N1 ACh receptor

41
Q

What NTs and receptors are present for parasympathetic nerve synapses?

A
Pre-ganglionic:
- NT: ACh
- Receptor: N2 ACh receptor
Post-ganglionic:
- NT:  ACh
- Receptor: M ACh receptor
42
Q

What NTs and receptors are present for sympathetic nerve synapses?

A
Pre-gaglionic:
- NT: ACh
- Receptor: N2 ACh receptor
Post-ganglionic:
- NT: NAd
- Receptor: Adrenergic receptors
43
Q

What NT and receptor is present for the sympathetic synapses to adrenal medulla?

A
  • NT: ACh

- Receptor: N2 ACh receptor

44
Q

What are the types of receptors present?

A
  • Ionotrophic: Ligand-gated ion channels (LGICs)

- Metabotrophic: G-protein coupled receptors

45
Q

What are the types of ACh receptors present?

A
  • Nicotinic: Ionotrophic; fast, excitatory.

- Muscarinic: Metabotrophic; slow, excitatory/inhibitory

46
Q

What does GABA stand for?

A

Gamma-amino butyric acid

47
Q

What are the glutamate receptors?

A
NMDA receptors:
- Fast excitatory
- Ionotrophic (Na+, K+, Ca2+)
AMPA receptors:
- Fast excitatory
- Ionotrophic (Na+, K+)
Kainate receptors:
- Metabotrophic
48
Q

What type of NT is glycine?

A

Inhibitory (opens Cl- channels)

49
Q

What are the GABA receptors?

A

GABA receptor A:
- Fast inhibitory (Opens Cl- channels)
GABA receptor B:
- Slow metabotrophic

50
Q

What factors influence the probability of APs in post-synaptic terminals?

A
  • Number of EPSPs
  • Number of IPSPs
  • Refractoriness of mebrane (affected by frequency of stimulation)
51
Q

Where are APs usually initiated in a neurone and why?

A
  • APs initiated at axon hillock

- Threshold is lowest here due to having the highest concentration of Na+ channels.