Receptors And Channels Flashcards
Receptor
A protein or group of proteins, usually embedded in cell membrane, allows cell to collect info about its surroundings
Ligand
A chemical messenger (can be small molecule or peptide) that induces a conformational change in the receptor
Conformational change
Change in shape of a receptor that induces some downstream signal transduction
2 main types of receptors
Ligand gated ion channels and G protein coupled receptors
2 main types of membrane bound receptors
Ligand gated ion channels
G protein coupled receptors
Cells that produce AP
Neurons, muscle cells, cardiac cells
Action potential purpose
How 3 types of cells communicate w each other
How APs are used to communicate
2 methods
APs propagate down axon of a neuron, jump from the end of one neuron to beginning of the next
Ligand gated and voltage gated ion channels
4 steps in Saltatory AP propagation
- AP occurred in initial segment, Na channel opening and in
- Local current makes depolarization brings axolemma at next node to threshold
- AP develops at node 2
- Local current produces depolarization that brings the 3rd axolemma at node to threshold
RMP
Inside of cell overall charge -70
Excitatory
Inside of a cells charge approaches 0 mv. Generally by letting + ions into cell
Inhibatory
Inside of cells charge becomes more neg, generally by letting neg ions (Cl especially) into cell
Depolarization
Excitatory, + ions into cell
Hyperpolarization
Inhibatory, - ions into cell
Agonist
A ligand that binds to a receptor and activates it
Antagonist
A ligand that binds to a receptor that prevents it from activation
Orthosteric antagonist
Acts on the main binding site of a receptor
Allosteric antagonist
Acts on accessory binding site of a receptor. Therefore agonist unable to go into main binding site.
Pore blocker
Physically obstructs the whole channel (ion channels). Nothing can go up or down.
Ligand gated ion channels
- transmission type
- composed of
Fast
Several subunits arranged around a central ion pore. Agonist binding opens pore.
Ligand gated ion channels
2 major families
Cys loop receptors and ionotropic glutamate receptors
Cys loop receptors 3 ex
Nicotinic acetylcholine receptor
Glycine receptor
5HT3 receptor
Ionotropic glutamate receptors
3 ex
AMPA
NMDA
Kainate
Cys loop receptors
Named for what
Loop formed by disulfide bond between 2 cysteines near the N terminus
Cys loop receptors
Composed of what
5 subunits arranged around a central pore. 5 subunits: 2 alpha, beta, gamma, delta
Excitatory cys loop receptors
Nicotinic acetylcholine
Serotonin
Inhibatory cys loop receptors
Glycine and gaba a
Ligand Gating
What allow things in
Agonist binding changes the conformation, moving the obstruction and allowing ions to flow through
Ligand gating
What blocks things
2nd transmembrane domain of the a subunit generally obstructs the ion pore
Drugs that work on ligand ion channels: cys loop
Nicotinic acetylcholine: nicotine, vareniciline (chantix)
Glutamate: NMDA receptors (ketamine), AMPA receptors (aniracetam- cognition enhancer)
Ex of cys loop receptor: nicotinic acetylcholine
- exists where
- contain what
- NMJ and in the CNS
- NMJ NAChR contain alpha, beta, delta, and gamma
- neuronal only contain alpha and beta
Ex of cys loop receptor: nicotinic acetylcholine
- what kind of conduction, ions passed
- composed of what
- what they do in brain in response to smoking
- excitatory- na, k, some ca
- 5 subunits
- nAChRs upregulate in response to chronic smoking
NAChR activation states
Can go interchangeably from closed, open, and desensitized
Longer ligand bound more of a chance of being desensitized
Ionotropic glutamate ligand receptors
- 3 types
- what they are/pass what
AMPA, NMDA, and kainate
-excitatory: pass na and k ions. NMDA can also pass ca ions
Ionotropic glutamate ligand receptors
- composed of what
- each subunit has what, NMDA in particular
- all must be what
- 4 subunits. Each one has 4 transmembrane domains. 2nd TM domain forms ion pore
- binding site- not all are for glutamate.
- NMDA- 2 binding sites for glutamate, 2 for glycine
- all 4 binding sites must be occupied for channel to open
Long term potentiation
The more often a neuron fires, the stronger the synapse gets. Implicated in learning and memory
At RMP, NMDA receptors are blocked by what. About this process
Mg ions. Mg block is voltage dependent. Depolarization of neuron relieves this block, allows NMDAR to open
NMDARs pass what, process of leading to stronger synapse. What these are also known as
Ca, activates CAMKII, leads to AMPARs inserted into synapse. More ampars= stronger synapse.
NMDARs= coincidence detectors
G protein coupled receptors
- rate of signaling
- role w genome
- target for what
- slower than ligand gated ion channels
- 3% of our genome dedicated to GPCR coding
- for more than 1/2 of current pharmaceuticals
GPCR classes
A- adrenergic receptors, muscarinic acetylcholine receptors
B- Parathyroid hormone receptor
C- metabotropic glutamate receptors, GABAb receptors
G protein activation
Alpha and beta gamma G proteins nearby. Alpha has GDP bound at rest. When receptor occupied by agonist recruits alpha, GTP replaces GDP. GTP causes alpha to go to target protein. GTP hydrolyzed back to GDP. Energy from this causes something to happen to target
Ga subunits
Gas
Gai
S- activation of adenylyl cyclase and increase in cAMP
I- inhibition of adenylyl cyclase and decrease in cAMP
Ga subunits
Gaq
Activation of phospholipase c, phosphoinositol hydrolysis, increase in IP3 and DAG, release of Ca from intracellular stores
GPCR desensitization
How it occurs
Independent of what
- if a ligand bound to GPCR for long period B-arrestin binds to receptor, tags it for internalization. Contributes to drug tolerance.
- GPCR B-arrestin complex can act as protein scaffold in the cell
- independent of G protein signaling
Cholera toxin mechanism
Cholera internalized by cell. Disrupts conversion of GTP to GDP. Inc level GTP leads to abn hi cAMP levels. Activates cl ion pumps, release more cl into interstitial lumen. Na, k, and hco3 ions follow, leading to more h20 held in intestine to balance osmolarity
