Second Messengers and VGICs Flashcards
What are the two types of postsynaptic receptors?
- Ionotropic
- Directly opens ion channels
- Metabotropic
- Works indirectly via metabolic changes to the postsynaptic cell to open ion channels
Describe ionotropic receptors.
- act as ligand-gated ion channels
- some can conduct multiple ions
- equally permeable to K+ and Na+
- Nicotinic Acetylcholine (ACh) receptor
- glutamate AMPA receptor (Ca2+)
- equally permeable to K+ and Na+
What are the two types of receptors for Acetylcholine (cholinergenc receptors)?
- nicotinic (ionotropic)
- muscarinic (metabotropic - linked to ion channel function via G-protein)
What are the fast receptors?
- Nicotinic (ACh)
- AMPA (Glu)
- Kainate (Glu)
- NMDA (Glu)
What are the slow receptors?
- Muscarinic (ACh)
- mGluR (Glu)
What is a second messenger?
- Intracellular molecules used to transduce an extracellular signal and produce a physiological change within the cell
- Signal amplification
- Signal regulation
Describe the effect of Ca2+ as a second messenger.
Upon stimulation of the cell, Ca2+ is able to enter the cell or be produced by the endoplasmic reticulum or even the mitochondria. The Ca2+ then goes on to have intracellular effects.
What is the structure of GPCR?
- Single polypeptide, the part that binds the NT
- Main function - activation of G protein
- 7 transmembrane domains
- ligands bind near extracellular domain
- several sytoplasmic domains near TM5, TM6, TM7 and maybe TM4 mediate G protein binding
- large protein superfamily
What are the three effects or second messenger cascades that the active G protein activates?
- Cyclic AMP
- Phospholipase C pathway
- can regulate ion channels (K+, Ca2+)
How do you inactivate a G protein?
- α subunit of G protein contains a GTPase
- GTP degraded to GDP
- α subinit reassociates with β and γ subunits
Describe the cyclic AMP cascade.
- G protein activates adenylate cyclase
- catalyzes conversion of ATP to cyclic AMP
- cyclic AMP activates protein kinase
- protein kinases phosphorylate other proteins
- activation of ion channels
- metabolic changes
- changes in transcription factors
How does phosphodiesterase terminate cAMP activity?
Converts cyclic AMP to 5’AMP
What does cGMP activate?
protein kinase G
Describe the phospholipase C pathway.
- common membrane molecule
- phosphotidylinositol 4,5-biphosphate (PIP2)
- NTs bind GPCR
- G proteins activated
- α subunit activates a membrane-bound enzyme
- phospholipase C (PLC)
- PLC catalyzes hydrolysis of PIP2 into inositol triphosphate (IP3) and diacylglycerol (DAG)
Describe the IP3 pathway.
- IP3 was the polar head of the phospholipid
- Freely diffuses into cytoplasm
- Releases Ca2+ from intracellular stores
- IP3R
Describe the DAG pathway?
- Nonpolar component of phospholipid
- Diffuses through the membrane bilayer
- Activates protein kinase C
- Results in protein phosphorylation
How does Ca2+ affect protein kinase C?
- Ca2+ released by IP3 can enhance activation of PKC
- Activating calmodulin
- calmodulin and Ca2+
- Activation of calcium/calmodulin-dependent protein kinases
- calmodulin and Ca2+
Describe the NO pathway.
- Highly diffusible
- can affect surrounding neurons
- short half-life
- Long term potentiation
How can signalling changes last a lifetime?
- Self-phosphorylation of protein kinases
- constitutively active
- Changes in gene expression
- metabolically or structurally change the cell’s response - permanently
In what way is there variety in VGICs?
Channel isoforms encoded by different genes. Each isoform has distinct functional characteristics.
Are voltage gated K+ channels highly diverse?
Yes. 18 genes encode for 50 isoforms in mammals.
Describe voltage-gates Na+ channels.
- Voltage gated Na+ channels are composed of 1 α subunit and 2 β subunits (1 β subunit in skeletal muscle).
- Each α subunit is made up of 4 domains
- Each domain has 6 membrane spanning regions
How does a Na+ channel sense a change in voltage?
At RMP and the channel is closed and the voltage sensors are positively charged and are poking into the cell. When the membrane depolarizes the transmembrane segments are pushed out of the cell which opens up the chnnel and allows Na+ to flow through it.
What are the two hypotheses for voltage gated Na+ channel inactivation?
- Ball and chain
- Hinged lid
Describe the movement of K+ through the VGIC.
Decribe how the presence of voltage gates Ca2+channels affects action potential.
- open at the same time or instead of voltage gated Na+ channels
- Ca2+ enters the cell causing depolarization
- Ca2+ influx slower and more sustained than Na+ influx
- Slower maximal frequency of APs due to longer refractory period
- Voltage gated Ca2+ channels play key role in function of cardiac muscle
