ion channels and g proteins Flashcards
3 steps of a signal transduction?
1) extracellular signal molecule activates membrane receptor
2) intracellular molecules transduced via a pathway
3) cell response activated
what is an extracellular signal? (Give examples)
A first messenger
- amines (adrenaline)
-steroid hormones
- proteins and peptides
what is an intracellular signal?
a second messenger molecule
what act as transducers between systems?
membrane proteins
4 classes of receptors?
ligand-gated ion channels
g-protein coupled receptors
enzyme-linked receptors
nuclear hormone receptors
what are ionotropic receptors?
ligand gated ion channels that form an ion pore
example of an ionotropic receptor
nicotinic acetylcholine receptor
Gaba A receptor
Stages of nicotinic Ach receptor?
1) binding of Ach opens channel for Na+
2) binding of nicotine
3) electrical event triggers response
4) calcium released
5) muscle contraction
What does Gaba A receptor inhibit?
inhibitor of neurotransmitters in CNS
What drug class activates Gaba A?
benzodiazepines
what are Gaba A receptors selective to?
chlorine ions
what are muscarinic receptors?(example)
type of Ach g protein coupled receptor
Examples of muscarinic receptors?
muscarinic ach receptor
Gaba B receptor- activated K+ channels
How many domains do GPCR have?
7 transmembrane domains
what are the 3 polypeptide chains of a g protein?
alpha, beta, gamma subunits
what does the alpha subunit bind to?
GTP/GDP
conditions of alpha-GDP?
resting condition - inactive g protein
high affinity to beta-gamma subunit
affinity of alpha-GTP?
low affinity to beta-gamma subunit
what does alpha subunit hydrolyse?
GTP to GDP
structure of PKA?
2 catalytic 2 regulatory polypeptides
what activates PKA?
binding of cAMP to R subunits
what happens when C + R subunits are bound?
R supresses activity of C so PKA is inactive
what happens when cAMP binds?
subunits dissociate
phosphorylation of other proteins allowed
what responses rely on cAMP/PKA pathway?
- kidney collecting duct
- vascular smooth muscle and cardiac muscle
- pancreas release of glucose
what hydrolyses cAMP?
phosphodiesterase (PDE)
what happens when cAMP unbinds?
increases R affinity to C
protein reassembles becomes inactive PKA
what inhibits PDEs?
caffeine so cell response is prolonged
PKA active for longer
what does desensitization of a receptor do?
feedback mechanism to reduce signal transduction
reduced cell response despite a sustained stimulus
Different alpha subunits of g protein?
alpha s
alpha i
alpha q
what does alpha s subunit do when activated?
simulates adenyl cyclase (AC)
uses ATP to produce cAMP
cAMP activates PKA
phosphorylation of target protein
what does alpha i subunit do?
inhibits AC
decreases cAMP
inactivates PKA
Receptor that couples to Gs?
beta2-adrenoreceptors - vasodilation decrease BP
vasopressin receptor
Examples of receptor that couples to Gi?
alpha2 adrenoreceptors
A1/3 adenosine receptors
M2 muscarinic receptor
Another class of g proteins?
Gq proteins with alpha q11 subunit
what do Gq proteins do?
allow activation of phospholipase C (PLC)
what does PLC do when stimulated by Gq protein?
cleaves PIP2 into IP3 and DAG
what is IP3 and what does it do?
water-soluble part - hydrophilic
travels through cytosol to stimulate calcium release from ER
promotes cell response
what does DAG do?
remains in membrane
recruits protein kinase C (PKC)
What are IP3, Calcium and DAG examples of?
second messengers
what are calcium mediated responses?
mediated by Ca2+ binding proteins
example of Ca2+ binding protein?
calmodullin CaM
what does CaM do?
binds 4 Ca2+ ions
complex activates PDE and CaM kinases (CaMKs)
what do CaMKs do?
phosphorylate serine and threonine residues on proteins
example of Gq protein receptor?
alpha 1 adrenoreceptor for vascular smooth muscle contraction
Vasoconstriction increase BP
Effects of DAG?
presence increases activity of Ca2+ dependent protein kinase
phosphorylates PKC
mediates desensitization
