Drugs and mutations targeting ion channels and their mechanism of action

Question 1

Please indicate the terminology used in the equation

I = ___________

n = _____________

Po = _____________

i = _________________

Answer 1

I = Whole-cell ionic current = the total amount of current flowing through the entire active population of that particular ion channel in a cell

n = number of ion channels in plasma membranes

Po = probability that any given channel in the plasma membrane is open

i = current through a single channel, single-channel conductance

Question 2

True or False

____ Voltage-gated ion channel function is dependent on how many channels are in the cell membrane (N), how many are open (Po), and how much current does each channel pass (i).

_____Permation(i) is highly regulated

___ Expression/trafficking determines n, which is highly regulated, there is short and long term regulation.

____ Activation and Inactivation gating are components of Po

Answer 2

True

False, Permeation is not highly regulated based on channels like an on/off switch

True

True

Question 3

Define Accelerators and brakes

Answer 3

Accelerators –> enhcnaces function

Brakes –> Prevent function

Question 4

Choose the correct options for the fundamental concept of accelerators and brakes

( Within ion channel / within neurons / within networks of neurons )

Accelerators: Voltage-sensor or ligand-binding domains allosterically coupled to activation gates

Brakes: Inactivates gates allosterically coupled to activation gates

Answer 4

Within ion channels

Question 5

Choose the correct options for the fundamental concept of accelerators and brakes

( Within ion channel / within neurons / within networks of neurons )

Accelerators: Trigger by electric activity, Na+, Ca2+ channels iGluRs, nACHRs

Brakes: K+ channels, Cl- channels, GABA-A receptors, Gly receptors

Answer 5

Within neurons

Question 6

Choose the correct options for the fundamental concept of accelerators and brakes

( Within ion channel / within neurons / within networks of neurons )

Accelerators: Primary excitatory glutamatergic neurons

Brakes: Primary inhibitory GABAergic neurons

Answer 6

within networks of neurons

Question 7

Phenytoin and lamotrigine are classical ion channel _________

they eliminate i

they (excitate/inhibit) the V.G. Na+ channels and neuornal excitability

Answer 7

blockers

inhibit

Question 8

True or False

Enhancement of GABA-A receptors and GABA mediated neuronal inhibition by benzodiazepines and barbituates increase Po

Answer 8

True

Question 9

_________- is a drug that enhances the V.G. K+ channels and neuronal inhibition (increase Po)

It is used for the treatment of epilepsy

Similar to benzodiazepines

Suppress A.P

Answer 9

Retigabine

Question 10

True or False

Tetrodotoxin binds in the selectivity filter of the Na+ ion channel, block the pore when the channel is in use (activate) and prevent Na+ to flow in.

Answer 10

False

It will block the pore no matter if the activation or inactivation gate is open

It is not a use-dependent drug

Question 11

__________ drug’s actions is based on how the ion channel is used.

Certain drugs bind within the channel and enter through the membrane or open pore.

These drugs can not access site of action when the channel is closed

if it acts as an agonist it will lock the protein in the open state

If it acts as an antagonist it will either lock in inactivated state or block pore

Answer 11

Use Depednece drugs

Question 12

Lidocaine is a great use dependence drug

True or False

___ Lidocaine is a high selectively inhibitory Na+ channel. It will only inhibit Na+ channels that are highly active.

____ The more usage of neurons the higher effect of blockage from Lidocaine.

Answer 12

Both are True

Question 13

Choose the correct options

(Gain-of-function mutation / Loss of function mutations )

yields increase ion channel activity

Higher expression levels of channels with the same gating characters

or

Normal expressing levels with altered gating leading to enhanced activity

It will increase cellular excitation in excitatory ion channels

Increased cellular inhibition in inhibitory ion channels

Answer 13

Gain of function mutation

Question 14

Choose the correct options

(Gain-of-function mutation / Loss of function mutations )

Yields reduced ion channel activity

reduced expression levels of channels with the same gating character

or

normal expression levels of channels with altered gating leading to reduced activity

It will decrease cellular excitation in excitatory channels

Decreased cellular inhibition in inhibitory channels

Answer 14

Loss of function mutations

Question 15

These Mutations in the Nav channel that are expressed in the brain result in _______ (3) and _______ (1)

SCN1A

SCN1B

SCN2A

SCN1A

Answer 15

Epilepsy

Migraine

Question 16

These Nav mutations expressed in muscle result in ________, _______, _________. Neuromuclar disorder

SCN4A

SCN4A

SCN9A

Answer 16

Myotonia

Periodic paralysis

Pain Erythema

Question 17

These ___, ____ mutations expressed in the cerebellar result in Cerebellar ataxia

Answer 17

K+ Ca2+

Question 18

Na 1.7 expressed in pain neurons

LOF ______________

GOF _________________

Answer 18

Insensitivity to pain

paroxysmal extreme pain disorder

Question 19

What are de novo pathogenic variants?

Answer 19

DNA changes that happen spontaneously showing up for the first time within a child ir unaffected parents.

Question 20

True or False

De Novo pathogenic variants are determined by a few methods looking at the whole genome, targeting sequencing and trio sequencing

Answer 20

True