Lecture 6 Flashcards
What gates Ion Channels? And how do they make effects
Ligands - neurotransmitters, drug agonists, or antagonists
Changes in voltage
G-proteins, 2nd messengers, phosphorylation
The frequency and duration of opening of the channel
Structure of Ion Channels
Ion channels are composed of subunits that are assembled into a channel. usually 4 or 5 subunits.
How can partial agonists effect opening of channels?
In the absence of any agonist, a partial agonist can increase the opening of a channel
In the presence of a full agonist, a partial agonist can actually decrease the opening of the channel
How can antagonists effect opening of channels?
In the absence of an agonist an antagonist generally has no effect on an ion channel
In the presence of a full or partial agonist, an antagonist will block the binding of the agonist and decrease the opening of an ion channel
In the presence of an inverse agonist an antagonist will slightly increase the opening of the channel
How can inverse agonists effect opening of channels?
Inverse agonists cause the channel to open very infrequently, and can cause the channel to become completely inactive.
Desensitization
Prolonged presence of an agonist can cause ligand-gated ion channels to desensitize or become unable to open even in the continued presence of an agonist
Even longer exposure can cause the channel to enter an inactive state that takes hours before opening again, even if the agonist is removed
PAM
positive allosteric modulators
PAMs bind to a site different from where the neurotransmitter binds and increase the opening of the channel only in the presence of the neurotransmitters.
What is the primary receptor for GABA? And what are some PAMs for the receptor?
GABA-A receptor
PAMs include benzodiazepines, barbiturates, alcohol, steroids and anesthetics.
NAM
Negative allosteric modulator
Bind to a site on the receptor different from where the neurotransmitter binds, and decrease the opening of the channel only in the presence of the neurotransmitters.
Name a class of drugs that targets voltage gated ion channels, and what kind of ion channels are targeted.
Anticonvulsant drugs such as lamotrigine block Na channels.
Local anesthetics such as novocaine, cocaine, and lidocaine block sodium channels and suppresses all local neuron activity.
What do enzymes bind? And what do they do to them?
Enzymes bind substrates, and change them, degrade, move, phosphorylate, dephosphorylate and then detach from the substrate.
What is an issue with enzymes as drug targets?
Enzymes are present in multiple cell types throughout the body, obtaining beneficial drug effects that are not toxic to other systems is difficult
Describe the difference between reversible and irreversible enzyme inhibitors?
Reversible enzyme inhibitors occupy the substrate site temporarily.
Irreversible enzyme inhibitors occupy the substrate site permanently
Name an example of a reversible enzyme inhibitor and how it works.
Donepezil (aricept) reversibly binds to AChE (acetylcholinesterase) to prevent the breakdown of ACh, which slows the cognitive decline in Alzheimer’s disease
Name an example of a irreversible enzyme inhibitor and how it works.
Nerve gases (sarin, VX,), venoms and insecticides irreversibly bind to AChE and cause convulsions, paralysis, and death
