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PMCOL 371 > 6 - Neuronal Ca+ Channels > Flashcards

6 - Neuronal Ca+ Channels Flashcards

1
Q

Five roles of Ca++ channels in excitable cells

A
  1. Intracellular signals
    1. Ca++ - dependent enzymes
    2. Gene regulation
  2. Transmitter release
  3. Electrical behaviour
    1. effects of Ca++ as charge carrier (intracellular messenger)
    2. Effects of Ca++ on other membrane ion channels
  4. Neurite outgrowth
  5. Muscle contraction
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2
Q

In the nerve fibre, the AP has only ____ and ____ components. How is this different from the nerve cell body, nerve terminal and muscle cell?

A

In the nerve fibre, the AP has only *Na+ *and K+ components.

The nerve cell body, nerve terminal and muscle cell, AP also has Ca++ component

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3
Q

Enzymes such as ____ and ____ are activated by Ca++ (intracellular messenger)

A

Enzymes such as protien kinases and proteases are activated by Ca++ (intracellular messenger)

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4
Q

Transmitter release is triggered by:

A

High [Ca++]

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5
Q

Why keep intracellular [Ca++] so low («100nM vs 2mM extracellular)
(4)

A
  • Maintain sensitivity
    • keep noise ⤓ , signal ⤒
  • Speed
    • Big gradient
    • fast, large, local increase in Ca++
  • Selectivity
    • activates only local processes, domain collapses rapidly
  • Safety
    • Ca++-sensitive processes only affected within domain
      - sensitivity can be low
      - prevents spurious activation by ambient Ca++
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6
Q

What is the importance of local [Ca++] in Ca++ domains?

A

locally high concentration (near Ca++ source) = local actions

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7
Q

What is the role of Ca++ channels in excitable cells?

A
  • in neuronal cell bodies, Ca++ enters through Ca++ channels while Na+ enters through Na+ channels during AP
  • Elevated [Ca++]i activated gK,Ca’s
  • BK channel (gK,Ca) repolarizes neuron during the AP
  • AK channel (IAHP) reduces repetitive firing
  • Involved in “bursting” behaviour
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8
Q

Role of Ca++ in excitable cells:

  • in neuronal cell bodies, Ca++ enters through ____while Na+ enters through ____during AP
  • Elevated [Ca++]i activates _____
    ____ repolarizes neuron during the AP
  • ____ reduces repetitive firing
  • Involved in “_____” behaviour
A
  • in neuronal cell bodies, Ca++ enters through Ca++ channels while Na+ enters through Na+ channels during AP
  • Elevated [Ca++]i activates gK,Ca’s
  • BK channel (gK,Ca) repolarizes neuron during the AP
  • AK channel (IAHP) reduces repetitive firing
  • Involved in “bursting” behaviour
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9
Q

What are Ca++ channels classified by?

A

Electrical behaviour and
Pharmacology

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10
Q

HVA (high voltage activated Ca++) channels start to activate near ___________

Include: ___, ___, ___, ___, __ channels

A

HVA (high voltage activated Ca++) channels start to activate near AP threshold (about -40mV)

Include: L-, N-, P-, Q-, R- channels

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11
Q

LVa (low voltage activated) Ca++ channels start to activate near ____

include ____ channels

A

LVa (low voltage activated) Ca++ channels start to activate near resting potential (-70mV)

include T channels

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12
Q

____ relationships distinguish Ca++ channels

A

I-V relationships distinguish Ca++ channels

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13
Q

Which Ca++ channels have single-channel properties?

A

T, N, L

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14
Q

Where are L-type Ca++ channels found?

A
  • Skeletal, cardiac muscle and to some extent in nerve
  • Conducting myocytes on AV/NA nodes
  • Lots in muscle - useful for biochemical studies (triggers Ca++ cascade rather than conduct Ca++)
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15
Q

L-type Ca++ channels are ____ activated

A

L-type Ca++ channels are high voltage activated (~-40mV)

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16
Q

L-type Ca++ have what role in muscles?

A

Act as a voltage sensor to trigger Ca++ cascadew

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17
Q

L-type Ca++ channels prefer to pass ____ rather than Ca++

A

L-type Ca++ channels prefer to pass Ba++ rather than Ca++

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18
Q

What are the pore-forming subunits in L-type Ca++ channels?

A

alpha1C and alpha1D

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19
Q

L-type Ca++ channels are blocked by most ____

As well as ____ and ______

A

L-type Ca++ channels are blocked by most dihydropyridines (nifedipine, nimodipine etc)

Hypertension

Also blocked by verapamil and inorganic blockers (Cd++, Co++, Ni++)

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20
Q

____ agonists such as BAYK-8644 will open L-type Ca++ channels

A

dihydropyridine agonists such as BAYK-8644 will open L-type Ca++ channels

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21
Q

L-type Ca++ channels are insensitive to most ____ (commonly used to identify presence of other Ca++ channels)

A

L-type Ca++ channels are insensitive to most toxins (conotoxins, agatoxins) (commonly used to identify presence of other Ca++ channels)

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22
Q

What increases opening probability of L-type Ca++ channels?

A
  • G-protein coupled agonists
    • esp beta-adrenergics
      • via a cAMP/protein kinase A mechanism
        - phosphorylate channel = increase opening probability
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23
Q

Where are N-type Ca++ channels most commonly found?

A

neurons

(not found in muscle)

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24
Q

Open time of N-type Ca++ channels vs L-type Ca++ channels?

A

N-type Ca++ channels have a shorter open time than L-type

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25
Q

Inactivation of N-type vs L-type Ca++ channels

A

N-type inactivate relatively rapidly compared to L-type

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26
Q

Pore of N-type Ca++ formed by ____ subunits

A

Pore of N-type Ca++ formed by* alpha1B* subunits

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27
Q

What toxins block N-type Ca++ channels?

A
  • omega-conotoxin G-VI-A
    - marine cone snail
  • omega-conotoxin M-VII-C
28
Q

N-type Ca++ channels are insensitive to ____, and ____ (which can block L-type Ca++ channels)

A

N-type Ca++ channels are insensitive to dihydropyridines, and omega-agatoxin-IV-A (spider) (which can block L-type Ca++ channels)

29
Q

What decreases the opening probability of N-type Ca++ channels?

A
  • G-protein coupled agonists
    • eg opioids, alpha2-adrenergics, GABAB agonists
30
Q

Mechanisms to decrease opening probability of N-type channels?

A
  • Direct, voltage sensitive interaction of G-protein betagamma subunits with channel
  • Indirect, voltage-insesntive modulation of the channel via second messengers
  • PRESYNAPTIC INHIBITION
31
Q

Unlike N-type and L-type Ca++ channels, T-type Ca++ channels prefer ____ over ____

A

Unlike N-type and L-type Ca++ channels, T-type Ca++ channels prefer Ca++ over Ba++

32
Q

T-type channels are ____-activated

A

T-type channels are low voltage-activated (LVA)

  • relatively negative voltage of activation
33
Q

T-type Ca++ channels have Rapid ____

A

T-type Ca++ channels have Rapid Inactivation

Only open for a short time

34
Q

T-type Ca++ channels require ____ to remove inactivation

A

T-type Ca++ channels require strong hyperpolarization to remove inactivation

35
Q

T-type Ca++ channels are important in ____of cells, not directly in transmitter release

A

T-type Ca++ channels are important in Burting behaviour of cells, not directly in transmitter release

36
Q

T-channels are formed from ____, ____ or ____ subunits

A

T-channels are formed from alpha1G, *alpha1H *or alpha1I subunits

37
Q

T-current bursting requires:

A

Opposing currents, offset in time

38
Q

T-type VDCC makes bursting possible when cell is ____

A

T-type VDCC makes bursting possible when cell is hyperpolarized

Does not affect cell when depolarized

Slow AP caused by T-current

39
Q

Which inorganic blocker is T-type VDCC most sensitive to?

A

Nickel (more so than Cd2+ or Co2+)

40
Q

T-type Ca++ channels are blocked by ____

A

T-type Ca++ channels are blocked by mibefradil

antihypertensive

41
Q

____ will block T-type VDCC at high concentrations

A

dihydropyridines will block T-type VDCC at high concentrations

42
Q

____ act as T-type channels

A

anticonvulsants act as T-type channels

  • Ethosuximide metabolites
    • mehtylphenylsuccinate-MPS
  • Phenytoin
  • ^^ block T-type channels
43
Q

T-currents can be modulated by ____

A

T-currents can be modulated by G-protein coupled agonists

  • Inhibition by Gbeta-gamma coupling
  • PKC family inhibits
    • Dopamine (DA), somatostatin, Angiotensin II
44
Q

P/Q-type Ca++ channel nomenclature arose from ____ where they were first described

A

P/Q-type Ca++ channel nomenclature arose from purkinje cells (large GABAergic cells of cerebellum) where they were first described

45
Q

P/Q type VDCC prefer conducting ____ over Ca++

A

P/Q type VDCC prefer conducting Ba++ over Ca++

46
Q

____forms pore of P/Q-type Ca++ channels

A

alpha1A forms pore of P/Q-type Ca++ channels

47
Q

P/Q-type VDCC’s are important in ____ of purkinje cell dendrites

A

P/Q-type VDCC’s are important in bursting behavior of purkinje cell dendrites

48
Q

Describe A-E

A

A - Na+ spikes alone

B- Na+ and Ca++ spikes

C - na+ firing eventually stops in presence of Cd++

D - Oscillatory Na+ and Ca++ responses

E - full trace of response in D

49
Q

P/Q-type VDCCs require ____ to deactivate

A

P/Q-type VDCCs require *relatively strong hyperpolarization *to deactivate

Inactivates rapidly

50
Q

What forms the pore of R-type VDCCs

A

Alpha1E

51
Q

R-type VDCC’s are resistant to:

A

Most toxins (conotoxins, agatoxins)

52
Q

R-type VDCCs are modulated by ____

A

some agonists

53
Q

VDCCs are made up of several subunits: ___, ___, ___, ___, ___

A

VDCCs are made up of several subunits: alpha1, alpha 2, beta, gamma, delta

54
Q

____ is the pore-forming molecule in VDCC’s

A

alpha1 is the pore-forming molecule in VDCC’s

Ten types of alpha 1 subunits

55
Q

Alpha1 subunit has ____ internal repeats, each with ____ transmembrane segments

A

Alpha1 subunit has four internal repeats, each with six transmembrane segments

56
Q

L-type Ca++ current go with which channels?

A
  • Cav1.1
  • Cav1.2
  • Cav1.3
  • Cav1.4
57
Q

P/Q currents are through which Ca++ channels/

A
  • Cav2.1
58
Q

N-current through which calcium channels?

A
  • Cav2.2
59
Q

R-current through which Ca++ channels?

A
  • Cav2.3
60
Q

T-current through which Ca++ channels?

A
  • Cav3.1
  • Cav3.2
  • Cav3.3
61
Q

beta subunit of VDCCs is ____ (ie no membrane spanning region)

A

beta subunit of VDCCs is hydrophilic (ie no membrane spanning region)

62
Q

effect of beta subunit of current (VDCC)

A

increases activation, decreases inactivation

63
Q

where a gamma subunits of VDCC’s found?

A

Skeletal muscle

64
Q

Effect of gamma subunit of VDCC

A

enhance activation; shift voltage of activation to more negative potentials

65
Q

delta subunit of VDCC is combined with ____

A

delta subunit of VDCC is combined with alpha 2

66
Q

In skeletal muscle alpha2-delta cleaved ____, then bound together with ____

A

In skeletal muscle alpha2-delta cleaved post-translationally, then bound together with disulphide bridges

PMCOL 371 (18 decks)

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