Session 5 - Electrical Excitability Flashcards Preview

Semester 2 - Membranes and Receptors > Session 5 - Electrical Excitability > Flashcards

Flashcards in Session 5 - Electrical Excitability Deck (51)
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1
Q

Give three structural similarities between Ca2+ ion channels and Na+ ion channels

A
  • 4 homogenous repeats which are linked together
  • Each repeat has 6 transmembranous domains one of which is voltage sensitive
  • The four repeats aggregate together to form a functional channel
2
Q

Name a main location where Ca2+ ion channels found

A

Nerve terminals

3
Q

Why does the internal concentration of Ca2+ change so significantly when Ca2+ ion channels open?

A

Because the concentration of Ca2+ inside is so low, the Ca2+ influx through Ca2+ channels is relatively very high.

4
Q

Give the sequence of events which causes neutransmitter release at nerve terminals

A
  1. Depolarization
  2. Voltage-gated Ca2+ channels open
  3. Ca2+ influx > down concentration gradient.
5
Q

Name the TYPE, BLOCKER and PRIMARY LOCATION of each isoform of Ca2+ ion channel

a1C,D,S

A

Type - L
Blocker - DHP
Primary location - All muscles, neurones, lungs

6
Q

Name the TYPE, BLOCKER and PRIMARY LOCATION of each isoform of Ca2+ ion channel

a1B

A

Type - N
Blocker - w-CTx-GVIA
Primary location - Neurones

7
Q

Name the TYPE, BLOCKER and PRIMARY LOCATION of each isoform of Ca2+ ion channel

a1A

A

Type - P/Q
Blocker - w-Aga-IVA
Primary location - Neurones

8
Q

Name the TYPE, BLOCKER and PRIMARY LOCATION of each isoform of Ca2+ ion channel

a1E

A

Type - R
Blocker - Ni2+
Primary location - Unknown (neurones, heart)?

9
Q

Name the TYPE, BLOCKER and PRIMARY LOCATION of each isoform of Ca2+ ion channel

a1G,H,I

A

Type - T
Blocker - Ni2+
Primary location - Neurones, heart

10
Q

What is the most common type of Ca2+ channel?

A

L type

11
Q

What is Nifedipine, and what does it do?

A

Nifedipine (a DHP) is used to control hypertension as it can act on vascular smooth muscle and prevent their constriction by blocking the L type Ca2+ channel. Ca2+ needed for contraction.

12
Q

What is the process via which neurotransmitters are released called?

A

Exocytosis

13
Q

In motor neurone terminals, what does increase in Ca2+ activate?

A

A group of proteins associated with the vesicle to promote exocytosis of ACh.

14
Q

Describe the process of events underlying fast synaptic transmission.

A
  • Depolarisation > voltage-gated ion channels open> Ca2+ influx
  • Ca2+ binds to synaptotagmin
  • Vesicle brought close to membrane
  • Snare complex (vesicle + protein) make a fusion pore
  • Transmitter released through this pore
15
Q

What is special about the location of Ca2+ in nerve terminals?

A
  • Ca2+ channels located close to vesicle release sites
16
Q

What happens to vesicle contents once released from the synapse?

A
  • ACh binds to nicotinic ACh receptor on the post-junctional membrane to produce an end-plate potential
  • Depolarisation, raises muscle above threshold so that an action potential is produced in the muscle membrane
17
Q

Give six properties of nicotinic acetycholine receptors

A
  1. Intrinsic pore
  2. Activated by binding of a chemical ligand (an atom, ion, molecule or radical which binds to a central atom forming a complex) to a site on the channel molecule e.g. ACh to site on nicotinic receptor
  3. Activation causes the pore to open
  4. Allows influx of Na+ into the cell
  5. Acetylcholinesterase breaks down ACh rapidly
  6. No binding of ACh > pore closed
18
Q

Name a competitive blocker of nicotinic receptors

A

Tubocurarine

19
Q

How does tubocurarine work?

A

Competitive blocker

  • d-tubocurarine (d-TC) binds to ligand site on receptor
  • ACh cannot bind > channel remains closed
  • Can be outcompeted by increasing ACh
20
Q

Name a depolarising blocker

A

succinylcholine

21
Q

How does succinylcholine work?

A

Depolarising blocker
* Bind to nicotinic receptors causing brief depolarisation which activate adjacent Na+ channels due to local current spread

  • Succinylcholine not hydrolysed by AChesterase
  • Maintatined depolarisation diminishes the ability of adjacent channels to recover from inactivation so they remain inactivated.
  • Local current can’t spread to other channels because they are too far away
22
Q

Name a disease which effect end plate receptors?

A

Myasthenia gravis

23
Q

What occurs in myasthenia gravis?

A
  • Antibodies directed against nAChR on post-synaptic membrane of skeletal muscle
  • Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degradation
  • End plate potentials reduced in amplitude leading to muscle weakness
24
Q

What drug is used to treat myasthenia gravis?

A

Acetylcholinesterase blockers

25
Q

What are the four ways in which basal Ca2+ levels are achieved?

A
  1. Relative impermeability of the plasma membrane to Ca2+
  2. The ability to expel Ca2+ across the plasma membrane using:feedback and Na+ - Ca2+ exchanger
  3. Ca2+ buffers
  4. Intracellular stores
26
Q

How does the ability to expel Ca2+ across the plasma membrane rely on a feedback mechanism?

A
  • [Ca2+]I increases
  • Ca2+ binds to calmodulin (trigger protein)
  • Ca2+/calmodulin complex binds to Ca2+-ATPase
  • Ca2+-ATPase removes Ca2+

High affinity, low capacity

27
Q

How does the ability to expel Ca2+ across the plasma membrane rely on a Na+-Ca2+ exchanger?

A
  • Secondary transport: [Na+] gradient used as driving force
  • Antiporter is electrogenic should work to removed Ca2+ best at resting potential

Low affinity, high capacity

28
Q

What role do Ca2+ buffers play in maintaining basal Ca2+ levels?

A
  • Ca2+ buffers limit diffusion
  • ATP and Ca2+ binding proteins e.g. parvalbumin, calsequestrin etc bind Ca2+
  • Many other proteins bind Ca2+ which alters their function – trigger – proteins e.g. synpatotagmin (synaptic transmission), calmodulin and troponin (contraction)
  • Depends on concentration of binding molecules and their level of saturation
29
Q

How is Ca2+ stored intracellularly?

A

Rapidly releasable
o G-protein coupled receptors (GPCRs)

o Ca2+ induced Ca2+ release (CICR)

Non-rapidly releasable

o Mitochondria

30
Q

What are two ways in which calcium can be elevated to alter function?

A
  1. Calcium influx across the plasma membrane
  2. Calcium release from rapidly releasable intracellular stores
  3. Calcium release from non rapidly releasable stores
31
Q

How can calcium be moved across plasma membrane?

A
  • Altered cell membrane permeability
  • Voltage gated calcium channels e.g synaptic bulbs
  • Receptor operated calcium channels e.g. some ligand gated nicotinic receptors
32
Q

How can Ca2+ be released from rapidly releasable stores?

A

G-protein coupled receptors

Ca2+induced Ca2+ release

33
Q

Where is calcium stored in rapidly releasable amounts?

A

Sacro/Endoplasmic reticulum by SERCA (sarco/endoplasmic reticulum Ca2+ ATPase). Ca2+ is moved in using the energyfrom ATP hydrolysis and bindsto protens such as Calsequestrin.

34
Q

How do G-protein Coupled Receptors work at calcium stores?

A

Ligand binds to the GPCR on the cell membrane, acivating its Gaq subunit.
This subunit binds to membrane phospholipid PIP2, releasing IP2, which binds to its receptor on sarcoendoplasmic reticulum, triggering release of Calcium

35
Q

How does CICR release Calcium?

Why is it important?

A

Ca2+ binds to theryanodine receptor on the side of the sarcoendoplasmic reticulum, triggering the release of calcium down its concentration gradient into the cell.

Important in cardiac myocytes - Ca2+enters cell via VGCC and binds to ryanodine receptor. This causes explosive release of Calcium ensuring strong, coordinated contraction

36
Q

Why would Ca2+ be taken up into mitochondria?

A

When Ca2+ is high as a protective mechanism - Also, to aid in buffering, regulating signalling and stimulation of ATP production.

37
Q

Why do mitochondria take part in normal Ca2+ signalling?

A

Due to microdomains (areas of cytoplasm with a high concentration of Ca2+ due to proximity to a channel).

38
Q

How do the mitochondria take up Ca2+?

A

Via the Ca2+ uniporter that is driven using respiration

39
Q

How are Ca2+ stores refilled?

A

By the recycling of cytosolic Ca2+ and by using Calcium stored in mitochondria.
Mitochondrial Ca2+ is used to replenish SR via the store operated Ca2+ channel (SOC)

40
Q

How does calcium assist in muscle contraction?

A

Binds to troponin, which undergoes a conformational change, causing tropomyosin to move and reveal binding sites

41
Q

What a return to basal levels of Calcium require?

A
  • Termination of signal
  • Ca2+ removal
  • Ca2+ store refilling
42
Q

How can Ca2+ be released from rapidly releasable stores?

A

G-protein coupled receptors

Ca2+induced Ca2+ release

43
Q

Where is calcium stored in rapidly releasable amounts?

A

Sacro/Endoplasmic reticulum by SERCA (sarco/endoplasmic reticulum Ca2+ ATPase). Ca2+ is moved in using the energyfrom ATP hydrolysis and bindsto protens such as Calsequestrin.

44
Q

How do G-protein Coupled Receptors work at calcium stores?

A

Ligand binds to the GPCR on the cell membrane, acivating its Gaq subunit.
This subunit binds to membrane phospholipid PIP2, releasing IP2, which binds to its receptor on sarcoendoplasmic reticulum, triggering release of Calcium

45
Q

How does CICR release Calcium?

Why is it important?

A

Ca2+ binds to theryanodine receptor on the side of the sarcoendoplasmic reticulum, triggering the release of calcium down its concentration gradient into the cell.

Important in cardiac myocytes - Ca2+enters cell via VGCC and binds to ryanodine receptor. This causes explosive release of Calcium ensuring strong, coordinated contraction

46
Q

Why would Ca2+ be taken up into mitochondria?

A

When Ca2+ is high as a protective mechanism - Also, to aid in buffering, regulating signalling and stimulation of ATP production.

47
Q

Why do mitochondria take part in normal Ca2+ signalling?

A

Due to microdomains (areas of cytoplasm with a high concentration of Ca2+ due to proximity to a channel).

48
Q

How do the mitochondria take up Ca2+?

A

Via the Ca2+ uniporter that is driven using respiration

49
Q

How are Ca2+ stores refilled?

A

By the recycling of cytosolic Ca2+ and by using Calcium stored in mitochondria.
Mitochondrial Ca2+ is used to replenish SR via the store operated Ca2+ channel (SOC)

50
Q

How does calcium assist in muscle contraction?

A

Binds to troponin, which undergoes a conformational change, causing tropomyosin to move and reveal binding sites

51
Q

What a return to basal levels of Calcium require?

A
  • Termination of signal
  • Ca2+ removal
  • Ca2+ store refilling