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neuropharmacology test 2 > test 2 lec one > Flashcards

test 2 lec one Flashcards

1
Q

Na+

A

inward current, Ratio _ 10:, made of 6 Transmembrane segments repeated 4 times and they all connected with a loop

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2
Q

Ca2+

A

inward current, Ratio _ 10k: 1

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3
Q

K+

A

outward current, Ratio _ 20:1

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4
Q

Cl-

A

inward current, Ratio _ 10.5:1

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5
Q

_ Ionophores

A

non-gated channels; they are protein that make a pore through the membrane and allow the ion to get in and out, some are selective and some are no, the only regulation is then just the size of the ion.

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6
Q

different kind of Ionophores

A

o Gramicidin: monovalent cations (the charge of one)
o Nystatin: monovalent cations
o Amphotericin: monovalent cations

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7
Q

what can probably move through ionophores

A

Sodium and potassium because they have only one positive charge

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8
Q

Monovalent

A

means the ion has only one charge. Ca2+ has charge of 2 so it is not monovalent.

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9
Q

ATPases (pumps)

A

can change membrane polarization because they move ion from one side to the other, That does not change the membrane potential of the cell to store the Ca2+ inside the calcium store

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10
Q

Na/K ATPase

A

this produce imbalance in the amount of charge, o Na and K ions act as cofactors for the exchange of the substrate (ATP) and the product (ADP), o 2 K from outside to inside are exchanged for 3 Na from inside to outside.

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11
Q

The resting potential

A

about -70 mV

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12
Q

Pump toxins which distrupt the pump’s function

A

_ Digitalis: come from plant source (very frequently used and prescribed as a drug) inhibits ATPase, _ Ouabain: comes from the plant sources, _ Thaspsigargin: Blocks Ca-ATPase of ER

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13
Q

endogenous Pump toxins

A

_ Ouabain: comes from the plant sources, found in adrenal cortex, endogenous in regions of CNS (glial cells)

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14
Q

_ Regional conformational change,

A

(only one portion of the structure changes it shape)

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15
Q

General conformational change

A

(the general change in the shape of the protein that makes up the ion channel) (in one state is close and one state is open)

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16
Q

Oldest of the gating models

A

General conformational change

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17
Q

Blocking particle

A

the basic shape remain unchanged.
o One attached subunit can move around and the new configuration block the opening of the ion channel or unblock and allow the passage of ion.

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18
Q

Three (or more) kinetic steps for ion channels to function

A

_ Closed state but ready to be activated, open, inactivate

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19
Q

gating models

A

Regional conformational change, General conformational change, Blocking particle

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20
Q

how is inactivation gate removed?

A

_ In order for the inactivation to be removed it requires repolarization of the membrane, it has to come back down to a negative state.

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21
Q

what happnes if we keep the membrane depolarized for a longer period of time?

A

It turns off, the term we use for that is _ it inactivates_ the inward current has inactivated even though we still continue to provide the voltage signal that was require to activate the current

22
Q

Channel structure conservation

A

o 6 Transmembrane segments repeated 4 times and they

23
Q

how can we change the function of a ion channel?

A

By doing a single amino acid substitution you can change the function of these channels, you can make them inoperable or change them from one channel to another,

24
Q

what is the activation or inactivation gate constitude of?

A

the lopps located on the extrace;llular and intracellular side of the membrane

25
Q

Na channel types?

A

Na channel types: NaV1.x the x part goes from 1 to 9. V means voltage gated. 1 means from one major gene family.

26
Q

what are the local anestethic that block the Na channels?

A

lydocaine (most commenly used) , _ Novocain: has too much risk associated with , Ropivacaine: Don_t diffuse very well so they stay local (not extremely lipophilic with the exception of cocaine)

27
Q

what is th initial compund of the lydocaine and Ropivacaine?

A

Cocaine

28
Q

what kiind of Na channel blocker is used by the dentist?

A

Lydocaine

29
Q

how does the Na channel blocker works?

A

they block the propagation of action potential. Then you wont get the message and you feel no pain. They inject it in the vicinity of the peripheral neuron and prevent it from getting to Brainstem

30
Q

what are some of the toxins that block sodium channels?

A

TTX, STX and QX-134

31
Q

TTX

A

made by Fugu Fish, very potent, Must apply to extracellular side of membrane not intracellular

32
Q

STX

A

it comes from red tide, which kills the fish, and if you eat the fish it kills you, o It has to be applied from the outside of the channel

33
Q

QX-314

A

much more expensive, but very small amount of it works, This drug works on the inside the membrane. Synthetic substance,

34
Q

how does a Cardiostimulant work?

A

stimulate by slowing the inactivation, prolong the activity of the open channel, as a consequence you get more current flow though the channel. _ Actually would be considered neurotoxins (because they slow) rather than a stimulant

35
Q

name 2 Cardiostimulant?

A

Aconitine, Veratridine

36
Q

_ Veratridine and _ Aconitine

A

it is considered neurotoxin, but it helps regulate heart rate in case weakened cardiac output

37
Q

why Cardiostimulants are not good?

A

they essentially blocks the information flow in to nervous system when neuron stay depolarize for that long, that_s why it is considered toxin

38
Q

_ Ca2+ influx

A

o VDCCs, glutamate receptor NMDA receptors is also a major source of the Ca2+ across the membrane

39
Q

_ Ca2+ stores

A

o CaBPs, ER, Mitochondria

40
Q

what is special about mitochondrial Ca2+ store?

A

most Ca2+ ends up here and is inaccessible except as one last grand event, as the cell dies, ex. apoptosis) you do not want the drug that activate mitochondrion Ca2+ channels

41
Q

_ Ca2+ release

A

o IP3Rs (as the mechanism that release Ca2+ into the cytosol but not into the cell it self.
o RyRs:Ca-dependent Ca2+-release)

42
Q

_ Ca2+ Efflux

A

ATPase, Na+-Ca2+ exchanger

43
Q

o Na+-Ca2+ exchanger

A

they are not pumps; they also contribute to disequilibrium of the membrane potential

44
Q

ATPase

A

to get raid of the extra Ca2+ in the cytosol. To pump the Ca2+ in to the store, also contribute to the hyperpolarization of the membrane potential.

45
Q

Ca2+ imaging

A

with fluorescent indicators, _ View concentration in axon and different types of neuron, o Fura-2 is most common used

46
Q

_ IP3 agonist

A

IP3, ATP act as an Activator also

47
Q

IP3 Antagonists

A

_ Heparin (is a good antagonist for IP3 receptors
_ Caffeine (mM) (moderate quantity of Caffeine is antagonist for IP3 receptor)

48
Q

_ Ryanodine agonist:

A

_ Ryanodine (mM) ( not endogenous)
_ Caffeine (mM): high level of caffeine is agonist.
_ Heparin (can have effect on smooth muscle on vascular system)
_ Ca2+: it binds to ryanodine receptor it activates the ion channels.

49
Q

Ryanodine antagonists:

A

Dantrolene: very effective at a very low concentration, _ Ryanodine, caffein: (high concentration mM is antagonist)

50
Q

Ryanodine activators:

A

_ Cytosolic Ca2+ (micro molar)
_ ATP (mM)

51
Q

different kinds of Ca2+ channels base on their voltage

A

o LVA: low voltage activating channels (does not take much depolarization to activate them)
o HVA: high voltage activation channels (take much larger depolarization to activate them)

neuropharmacology test 2 (8 decks)

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