GPCRs Flashcards
- dissociates into active subunits (that interact w. downstream targets [effectors])
- return to resting state when GTP is hydrolysed into GDP (& phosphate)
What is the function of GPCRs?
Produce smaller, longer-in-duration & more widespread responses!
Gs =
Gi =
Gt =
Go =
Gq =
Gs = stimulates adenylyl cyclase
Gi = inhibits “ “
Gt = transducin (in retina) activates phosphodiesterase
Go = regulates ion channels
Gq = couples to phospholipase
How many levels of regulation by G-proteins are there?
3
What is the first level of regulation by G-proteins?
- DIRECT MODULATION of channel function by binding of a G-protein
What is the second level of regulation by G-proteins?
- Modulation by synth. of a SECOND MESSENGER that binds to the channel
What is the third level of regulation by G-proteins?
- Modulation by 2nd MESSENGER-MEDIATED ACTIVATION of a KINASE that phosphorylates the channel
Give an example of direct modulation of channel function by binding of a G-protein.
The M channel of cardiac atrium is regulated by the mAChR (muscarinic ACh receptor)!
FUNCTIONAL SIGNIFICANCE: Parasympathetic stimulation of the heart slows the rate!
Parasympathetic fibres (vagus nerve) release ACh onto cardiac atrial muscle cells
Give an example of modulation by synth. of a second messenger that binds to the channel.
SIGNAL TRANSDUCTION IN RETINA!
FUNCTIONAL SIGNIFICANCE: The mechanism for the detection of light in the vertebrate visual system.
“Dark current”: A continuous depolarising current flows through cGMP-gated cation channels in membranes of photoreceptors in the dark.
In response to light, decreased cGMP and closure of the channels causes hyperpolarisation of the photoreceptor cell.
The decrease in transmitter release is interpreted by the CNS as the detection of light
Discuss Photoreceptor signaling.
A photon (hv) is absorbed by a rhodopsin GPCR, thus activating the G-protein transducin.
The GT subunit activates phosphodiesterase (PDE), to breakdown cGMP into inactive GMP.
cGMPgated cation channels close.
Give an example of modulation by 2nd messenger-mediated activation of a kinase that phosphorylates the channel.
Increase in the rate and force of contraction in the heart!
FUNCTIONAL SIGNIFICANCE: The sympathetic nervous system prepares the body for a “fight or flight” response, which includes an increase in cardiac output.
e.g. sympathetic signaling in cardiac muscle
Discuss sympathetic signaling in cardiac muscle
Adrenaline binds to an adrenergic GPCR,
– activates a G protein, which
– regulates adenylate cyclase (an enzyme) which
– increases the synthesis of cAMP.
cAMP activates PKA, a protein kinase that phosphorylates voltage-gated Ca channels,
increasing their open probability,
and thus increasing the intracellular Ca,
promoting cardiac muscle contraction.
Enhanced Ca channel activity is seen as an increase in the duration of the plateau,
corresponding to an increase in Ca influx
and increased tension generation (strength of contraction).
