BB Lecture 20: Channel Regulation by Second Messengers Flashcards
What are “third messengers”?
protein kinases and phosphatases
What are triggers for release of Ca2+?
inositol triphosphate (IP3 receptor)- predominately ER Ca2+ (ryanodine receptor; RyR)- both ER and SR
How does IP3 increase cytoplasmic concentration of Ca2+?
activation of specific G protein-coupled receptors or receptor tyrosine kinases that stimulate phospholipase C (PLC)
this cleaves PIP2 into two different second messengers (diasoglycerol + IP3)
IP3 diffuses into cytoplasm and reaches ER membrane where it can bind its receptor
induces conformational change and opens Ca2+ channel
How does the RyR mechanism increase cytoplasmic concentrations of Ca2+?
Ca2+ binds cytoplasmic site of a Ca2+ channel (e.g. voltage-gated Ca2+ channel, nAChR channel, or NMDA-type glutamate receptor) opening it
released Ca2+ activates the RyR which can further propogate the release of Ca2+ resulting in amplification of Ca2+ signal
How is the RyR regulated?
inactivated by high concentrations of Ca2+
How does the activation of PLC affect K+ channels?
PLC generates IP3 and depletes PIP2
PIP2 has a negatively charged head group available to interact wiht positively charged regions of proteins near the membrane
voltage-gated K+ channels are inactivated by their positively charged “ball” subunit blocking the pore but PIP2 can bind the ball so that it can’t inactivate the pore
leads to slow inactivation of K+ channels
What is the dark current?
flows through the inner and outer segments of a photoreceptor (rods and cones)
inner segment regulated by K+ channels (primer membrane conductance)
outer segment controlled by Na+ and Ca2+ channels whose conductance is max in darkness (keep V around -40 mV in darkness)
current flows from outer to inner segments due to charge repulsion
How are the ion gradients maintained in rods/cones?
Na+/K+ ATPase (inner segment)- maintains K+ and Na+ gradients
Na+/Ca2+ antiporter- removes Ca2+ from the cell
Describe how second messengers act on the cones/rods.
Na+/Ca2+ channel in the outer segment is gated by cyclic guanosine monophosphate (cGMP)
light determines the level of cellular cGMP (more light less cGMP)
Describe the process of phototransduction.
photon activates rhodopsin (G protein-coupled receptor)
this stimulates GDP-GTP exchange by transducin (a G Protein)
activates cGMP phosphodiesterase which hydrolizes cGMP
reducing cGMP decreases the current flowing through the cMGP-gated channels in teh outer segment
dark current diminished
membrane hyperpolarized
What is the difference between the activity of the alpha subunit of a GPCR and the beta-gamma subunit?
alpha- generates a second messenger to communicate with cytoplasmic enzymes
beta-gamma- acts within the plane of the membrane (operates only over very short distances within the bilayer to open some channels within that distance)
What is a GIRK?
G protein-regulated inward rectifying K+ channel
a K+ inward rectifying channel that is opened by acetylcholine (mediated by G-beta-delta subunit)
very fast increase of activity
