Lecture 2: Membrane Bound Receptors Flashcards
Resting Membrane Potential Amount
-70 mV
Excitatory
inside of cell approaches 0 mV
Inhibitory
inside of cell becomes more negative
usually lets Cl into cell
Orthosteric antagonist
binds to main binding site of receptor
can be outcompeted
Allosteric antagonist
binds to accessory binding sites
Pore blocker
physically obstructs the channel
Ligand gated ion channels speed and families
fast
cys-loop receptors
ionotropic receptors
Cys-Loop receptor shape
pentamer - up to 5 subunits
Cys-Loop excitatory receptors
nicotinic acetylcholine receptors
serotonin receptors
**Inhibitory receptors
Glycine
GABAa
What obstructs the pore of ligand gated ion channel
second transmembrane domain of alpha subunit
Cys-Loop receptor drugs (nicotinic and GABAa)
nicotinic acetylcholine receptors - nicotine, varenicline (chantix)
GABAa receptors - barbiturates, benzodiazepines, alcohol
Glutamate receptor drugs
NMDA receptors - ketamine
AMPA receptors - Aniracetam
Nicotinic Acetylcholine Receptors
NMJ - alpha, beta, delta, gamma
neuronal - alpha, beta
up-regulate in response to chronic nicotine (x2)
**Desensitized state
higher affinity for ligand to bind
E.g. Smoker that’s jittery
administer nicotine to move channel from open to desensitized
Ionotropic glutamate receptor size, type, what do they pass?
tetramers, excitatory, pass Na, K ions
IGlu receptors: NMDA can pass what ions through?
Ca ions
NMDA binding sites
4 sites: 2 glutamate, 2 glycine, all 4 must be occupied
Long term potentiation
IGlu receptors do this.
more often neuron fires, stronger the synapse (learning, memory)
NMDA receptor blockage
blocked by Mg (pore blocker) at resting membrane potential, voltage dependent
When NMDA receptor opens:
Ca passes through, activates CaMKII
AMPAR inserted in synapse, stronger synapse
What are coincidence receptors?
NMDA receptors because you need successive activation
G protein coupled receptor speed and classes
slower than ligand gated ion channels, Class A, B, C
GPCR class A
adrenergic, muscarinic acetylcholine
GPCR class B
parathyroid hormone
GPCR class C
metabotropic glutamate, GABAb
G alpha subunit Gas
activation of adenylyl cyclase, increase cAMP
G alpha subunit Gai
inhibition of adenylyl cyclase, decrease cAMP
G alpha subunit Gaq
activation of phospholipase C, phosphoinositol hydrolysis, increase IP3 and DAG, release of Ca from intracellular stores
GPCRs affect:
enzymes, transport proteins, contractile proteins, ion channels
How does Cholera toxin work
disrupts GTP to GDP path increased GTP - high cAMP high cAMP activates Cl ion pumps Cl leaves cell into intestines Na, K, HCO3 follow Cl, hyperosmolarity, water follows
GPCR desensitization
if ligand bound for long time, beta arrestin tags receptor, cell internalizes receptor, drug tolerance ensues
GPCR beta arrestin complex
act as protein scaffold, independent of G protein signaling
