Chapter 3: Ion channels

Question 1

what ions do the most important ion channels regulate

Answer 1

calcium
sodium
chloride
potassium

Question 2

what are ion channels made of

Answer 2

subunits of amino acids assembled around an ion channel

Question 3

what 2 things regulate the sensativity of channel opening

Answer 3

neurotransmitters
allosteric modulators

Question 4

structure of pentameric ionotropic receptors

Answer 4

5 subunits of 4 transmembrane regions

Question 5

where are the receptor sites on each subunit

Answer 5

some are inside the channel and some are allosteric

Question 6

Types of pentameric ionotropic receptors

Answer 6

GABAa receptors
Nicotinic cholinergic receptors
serotonin 5HT3 receptors
certain glycine receptors

Question 7

neurotransmitters that act directly on pentameric ionotropic receptors

Answer 7

acetylcholine (nicotinic)
GABA (GABAa)
glycine (strychnine-sensative)
serotonin (5HT3)

Question 8

natural neurotransmitters v. drugs on pentameric ionotropic receptors

Answer 8

neurotransmitters bind to every subtype and drugs may bind selectively to 1 or more subtypes

Question 9

structure of tetrameric ionotropic receptors

Answer 9

4 subunits that contain 3 transmembrane regions and 1 entrant loop

Question 10

where are the 4 re-entrant loops on tetrameric ionotropic receptors

Answer 10

they line the ion channel

Question 11

types of tetrameric ionotropic receptors are

Answer 11

Glutamate receptors:
AMPA
Kainate
NMDA

Question 12

action of full agonists on ionotropic receptors

Answer 12

open ion channel to max frequency for max downstream signal transduction

Question 13

what increases opening of ion channel greater than full agonist

Answer 13

presence of a PAM

Question 14

action of antagonist on ionotropic receptors

Answer 14

stabilizes receptor in its resting state (constitutive activity) despite the presence or absence of an agonist

Question 15

what do antagonists reverse

Answer 15

full agonist
partial agonist
inverse agonist

Question 16

action of partial agonist on ionotropic receptors

Answer 16

opens channel greater than constitutive activity but not as great as full agonist depending on how close it is to the full agonist/antagonist

Question 17

action of an inverse agonist on ionotropic receptors

Answer 17

closes channel completely (less action than constitutive activity)

Question 18

can inverse agonist be distinguished clinically from an antagonist

Answer 18

not clear

Question 19

what are the different states of ionotropic receptors

Answer 19

desensitization and inactivation

Question 20

what is desentiziation of an ionotropic receptor and what causes it

Answer 20

when the ion channel quits responding to the agonist over time due to over or prolonged stimulation.
quickly reversible

Question 21

what is inactivation of an ionotropic receptor and what causes it

Answer 21

same as desensitization, however, it is one step past so it takes several hours after agonist is gone before it returns to its resting state and can again be stimulated by the agonist

Question 22

what is an allosteric modulator

Answer 22

ligands that bind to sites other than where the neurotransmitters bind

Question 23

what is a PAM and what does it do

Answer 23

positive allosteric modulator
when it binds to its allosteric site when the agonist is bound it increases the opening more than the full agonist alone

Question 24

what is a NAM and what does it do

Answer 24

negative allosteric modulator
when it binds to its allosteric site while the neurotransmitter is bound it blocks or decreases the action of the neurotransmitter (agonist)

Question 25

example of PAM

Answer 25

benzodiazepines boost the action of GABA at chloride ion channels

Question 26

example of NAM

Answer 26

NAM for NMDA: phencyclidine ketamine

Question 27

when do allosteric sites have PAM action

Answer 27

when the ligand is a full agonist

Question 28

when do allosteric sites have NAM action

Answer 28

when the ligand is an inverse agonist

Question 29

which neurotransmitters work on pentameric ionotropic receptors

Answer 29

acetylcholine GABA serotonin

Question 30

which neurotransmitters work on tetrameric ionotropic receptors

Answer 30

glutamate

Question 31

examples of drug classes that act on GABA pentameric ionotropic receptors

Answer 31

benzodiazepines Z drugs/hypnotics (zolpidem, zaleplon, zopiclone, eszopiclone) neuroactive steroids

Question 32

examples of drugs that act on serotonin pentameric ionotropic receptors

Answer 32

mirtazepine vortioxetine anti-emetics

Question 33

example of drugs that work on glutamate tetrameric ionotropic receptors

Answer 33

PCP ketamine dextromethorphan dextromethadone

Question 34

what regulates opening of voltage-sensitive ion channels

Answer 34

the charge/voltage across the membrane

Question 35

first phase of opening voltage-sensitive ion channel

Answer 35

voltage-sensitive sodium channels open and sodium rushes downhill into the negatively charged, sodium-deficient neuron

Question 36

second phase of opening a voltage-sensitive ion channel

Answer 36

influx of sodium changes the voltage of the neuron which triggers the opening of voltage-sensitive calcium channels and calcium rushes in

Question 37

third phase of opening a voltage-sensitive ion channel

Answer 37

once action potential is gone, potassium enters neuron and sodium is pumped out which restore electrical milieu back to baseline

Question 38

what makes up the "pore" of VSSCs

Answer 38

when 4 amino acid subunits with sodium ionic filters come together to form the hole in the middle

Question 39

what makes up the "pore" of VSCCs

Answer 39

when 4 amino acid subunits with calcium ionic filters come together to form the hole

Question 40

what is the pore called on VSSCs

Answer 40

subunit a

Question 41

what is the pore called on VSCCs

Answer 41

subunit a1

Question 42

which transmembrane proteins flank subunit a (pore) of VSSCs and what do they do

Answer 42

B units and their function is not clearly established

Question 43

how many transmembrane regions are on the amino acid subunits that make up VSSCs and VSCCs

Answer 43

6

Question 44

which transmembrane segment detects the difference in charge across the membrane of voltage-sensitive ion channel subunits and why is that important

Answer 44

transmembrane segment 4 alerts the rest of the protein when it senses a change in charge which triggers conformational changes that open/close the channel

Question 45

where is the extracelluar loop on voltage-sensitive ion channel subunits and why is it important

Answer 45

between transmembrane segments 5 and 6 functions as a filter to either allow sodium (VSSC) or calcium (VSCC) to enter

Question 46

how are the subunits of voltage-sensitive ion channels connected

Answer 46

by connector loops

Question 47

what is the significance of the connector loop between transmembrane units 3 and 4

Answer 47

act as a plug to close the channel

Question 48

what are the three states of voltage-sensitive ion channels

Answer 48

open and active inactivated closed and inactivated

Question 49

open and active state of voltage-sensitive ion channels

Answer 49

allow max flow of ions across the membrane

Question 50

inactivated state of voltage-sensitive ion channels

Answer 50

loop goes into pore to stop the flow of ions immediately (before channel is even closed)

Question 51

closed and inactivated state of voltage-sensitive ion channels

Answer 51

when there are conformational changes in the ion channels shape that closes it

Question 52

what is the pore called on VSCCs

Answer 52

subunit a1

Question 53

extracellular proteins that flank subunit a1

Answer 53

y (spans the membrane) B (cytoplasmic units) a2ẟ

Question 54

pregabalin and gabapentin target which extracellular protein of VSCCs

Answer 54

a2ẟ

Question 55

types of VSCCs

Answer 55

N or P/Q channels L channels R and T channels

Question 56

N or P/Q channels of VSCCs

Answer 56

presynaptic regulators of neurotransmitter release

Question 57

what is the "snare" in VSCCs

Answer 57

the amino acid loop that connects the 2nd and 3rd subunits work as a “snare” to hook to the synaptic vesicle to regulate the release of the neurotransmitter into the synapse during neurotransmission

Question 58

how does the molecular "snare" work in N or P/Q voltage-sensitive ion channels

Answer 58

If a drug interferes with calcium entering the cell then the vesicle stays tethered to the channel and neurotransmission is prevented. When calcium enters the cell, the snare docks with the vesicles and moves it to the synapse so the neurotransmitter can spill into it.

Question 58

how does the molecular "snare" work in N or P/Q voltage-sensitive ion channels

Answer 58

If a drug interferes with calcium entering the cell then the vesicle stays tethered to the channel and neurotransmission is prevented. When calcium enters the cell, the snare docks with the vesicles and moves it to the synapse so the neurotransmitter can spill into it.

Question 59

what is another term for the work of the snare in N or P/Q voltage-sensitive ion channels

Answer 59

excitation-coupling

Question 60

Where do L channel VSCC reside

Answer 60

in the CNS but also on vascular smooth muscle

Question 61

R and T channel voltage-sensitive ion receptors

Answer 61

exact roles being clarified some anticonvulsants and psychotropic drugs interact here

Question 62

discuss ion channels and neurotransmission

Answer 62

neuron receives info from previous neuron and encodes it into an action potential. the impulse is sent down the axon via VSSCs. when the impulse reaches the axon terminal it meets VSCCs in the presynaptic membrane. when the voltmeter in the VSCC detects the impulse they open to allow calcium into the neuron. Then neurotransmitter is released into the synapse