Membrane-Bound Receptors Flashcards
What are receptors
a way in which cells can communicate with each other and gain information about the area around them
2 types of receptors
ligand-gated ion channels and G protein coupled receptors
What binds to the receptor
ligands, which are a chemical messenger
What does a ligand do when it binds
induces a conformational change in the receptor tell the cell something about its environment. The receptor changes shape and tells downstream to do something.
what cells produce Action Potentials
neurons, muscle cells, and cardiac cells
-how these cells communicate with each other
How does the AP communicate and what starts in and keeps it going
the AP propagates down the axon of a neuron and jumps from the end of on neuron to the beginning of the next. -the ligand-gated ion channel starts the AP
-Voltage-gated ion channels propagate the signal
Excitatory
the inside of the cells charge approaches 0mV getting less negative
-Depolarization
Inhibitory
the inside of the cells charge becomes more negative, further away from creating an AP
-Hyperploarization
Resting membrane potential
inside of the cell has an overall negative charge of -70mV
Agonist
a ligand that binds to a receptor, thereby activating it
Antagonist
a ligand that binds to a receptor that prevents it from activating
Orthosteric Antagonist
Acts on the main binding site of the receptor, blocks the agonist from the binding site
Allosteric antagonist
acts on an accessory binding site of the receptor
-changes the receptor shape so the agonist can’t bind, doesn’t fit
Pore blocker
physically obstructs the channel
Ligand-Gated Ion Channel
- fast transmission
- composed of several subunits arranged around a central ion pore
- agonist binding opens pore
Ligand-Gated Ion channel families
- cys-loop receptors
- Ionotropic Glutamate Receptors
Cys-loop receptor types
- nicotinic ACh receptor
- glycine receptor
- 5HT-3 receptor
Ionotropic Glutamte receptor types
- AMPA receptor
- NMDA receptor
- Kainate receptor
Cys-Loop receptors
- have a loop thats formed by a disulfide bond between two cysteine near the N-terminus
- Made of 5 subunits arranged around a central pore: alpha, beta, gamma, delta, epsilon
cys-loop excitatory
Nicotinic-ACh
Serotonin
Cys-loop inhibitory
Glycine and GABAa
Gating
This is what causes the ion pore to be closed
- the second transmembrane of the alpha subunit is what forms the gate
- agonist binding changes the conformation, moving the obstruction (gate) allowing ions to flow through
drugs that act on cys-loop receptors
- nicotinic-ACH: nicotine, Carenicline (chantix)
- Barbituates, benzos, alcohol, ambien
drugs that act on Glutamate receptor
NMDA receptors: Ketamine
AMPA receptors: Aniracetam (cognition-enhancer)
Nicotinic-ACH receptor
exist at the neuromuscular junction (NMJ) and in the CNS
- composed of 5 subunits
- NMJ nAChR contains alpha, beta, gamma, and delta
- Neuronal nAChRs contain only alpha and Beta subunits
- in the brain nAChRs upregulate in response to chronic nicotine like smoking
nAChR excitatory
pass Na, K, and some Ca ions
Iontropic Glutamate Receptors
- AMPA
- NMDA
- Kainate
- composed of 4 subunits
- -each subunit has 4 transmembrane domains and the 2nd transmembrane forms the ion pore
- each subunit has a binding site-not all binding sites are for glutamate
Iontropic Glutamate Receptors, excitatory
pass Na and K ions
NMDA receptors can also pass Ca ions
NMDA receptor binding sites
2 binding sites for glutamate, 2 binding sites for glycine
-all 4 binding sites must be occupied for the channel to open.
long term potentiation
the more often a neuron fires the stronger the synapse gets
NMDA receptors at resting membrane, and what happens when activated
NMDAr are blocked by Mg
- Mg is voltage dependent
- depolarization of neuron relieves the block, allows NMDAr to open
- When open Ca can pass which activates Ca calmodulin Kinase II
- which leads to AMPARs being inserted into the synapse
- more AMPARs=stronger synapse
- NMDARs are “coincidence detectors”
G-Protein-Coupled receptors (GPCR)
slower signaling that ligand-gated ion channels
- relay on 2nd messenger
- 3% of our genome dedicated to GPCR coding
- *target for more than 1/2 of current drugs
GPCR classes
A:adrenergic receptors, muscarinic acetylcholine receptors
B:Parathyroid Hormone receptor
C: metabotropic glutamate receptors, GABAB receptors
G-Proteint activation
- ligand binds to receptor
- GDP is traded for a GTP on the alpha subunit
- Beta/gamma break off
- Alpha and GTP activate target protein
- activation is terminated when GTP is hydrolyzed to GDP
G alpha S
activation of adenylyl cyclase and increase in cAMP
G alpha I
inhibition of adenylyl cyclase and decrease in cAMP
G alpha Q
activation of phospholipase C, phosphoinositol hydrolysis, increase in IP3 and DAG, and release of Ca2+ from intracellular stores
Downstream targets of GPCR
- Target enzymes: Adenylate cyclase and phospholipase C
- 2nd messengers: cAMP, IP3, DAG
- Protein kinases: PKG, PKA, PKC
- Effectors: enzymes, transport proteins, contractile proteins, Ion channels
GPCR desensitization
if a ligand is bound onto a GPCR for a prolonged time it is phosphorated by a specific kinase
- Beta-Arresting binds to the receptor,
- causing it to loose its ability to associate with G-protein, which tags it for internalization
- undergoes endocytosis which removes its receptor fro the membrane.
- -this contributes to drug tolerance
GPCR-beta arrestin
can act as a protein scaffold inside the cell. Contains the GPCR
-this is independent of G protein signaling
Cholera Toxin Mechanism
- cholera toxin is internalized by the cell
- disrupts conversion of GTP to GDP (blocks GTPase activity preventing inactivation)
- increases level of GTP leads to abnormally high cAMP levels
- -this activates Cl ion pumps which release more Cl into the investing lumen
- -Na, K and bicar ions follow–leading to more water being held in the intestine to balance osmolarity
