rec- structure and signalling (main focus on proteins)

Question 1

importance of ca2+ in the cytoplasm (7 answers, get main 4)

Answer 1

1. cell signalling- binding of another molecule to receptor may cause ion cascade
2. muscle contraction- AP along membrane, release of stored ca2+= binding to contractile PROTEINS
3. neurotransmitter release in presynapse
4. cell communication
5. gene expression and regulation
6. cell cycle
7. apoptosis

Question 2

structure of TMPs

Answer 2

2+ alpha-helicies
2-6 subunits that surround the pore (usually w/ exceptions like ammonia (?) and Chlorine)

Question 3

2 reasons for ion selectivity

Answer 3

size of the filter
and AMINO ACID linings of the pore

Question 4

AMINO ACID selectivity in pores

Answer 4

Size- smaller molecules dont have to interact with the aa’s
aa’s on negatively charged chains will react positively with positively charged ions, but repel the negatively charged ones

Question 5

which side of the TM is tighter, and therefore creating a ‘gate’

Answer 5

cyctoplasmic side

Question 6

difference between the groups of ions, Na+, K+ and Ca2+

Answer 6

Na+ and K+ create APs in excitable cells
Ca2+ transported into cytoplasm where 2nd messenger elicits cell response- cascade etc

Question 7

3 differences to a simple ion channel

Answer 7

1. additional helices S1 and S4- form a separate ‘voltage sensing domain’ lateral to subunits
2. Large polypeptide extends into cytoplasm
3. plugging mechanism

Question 8

TRPs sense what stimuli= 2

Answer 8

physical stimuli and chemical

Question 9

2 types of ligand gated ion channels=

Answer 9

intracellular ligand and extracellular ligands

Question 10

example of how ligand gated ions channels can cause seizures?

Answer 10

mutation in nAChR causing autosomal dominant nocturnal frontal lobe epilepsy

Question 11

how the nAChR work and what goes wrong

Answer 11

1. ACh conc depends on use of use-dependent potention
   the delay in the rising phase of the mutant ACh response= caused by slow unblocking of the CLOSED mutant rec

Question 12

Glutamate acts in what part of the body

Answer 12

the brain, as the main neurotransmitter

Question 13

uniqueness of the NMDA-glutamate receptor

Answer 13

role in synaptic plasticity, learning and memory

Question 14

structure of the NMDA-glutamate receptor- and its importance

Answer 14

voltage dependence activation
high calcium permeability
involvement in long-term potentiation and long term depression- synaptic plasticity

Question 15

regulation and specificity of the Glut-NMDA rec

Answer 15

VOLTAGE DEPENDENCE AND THE MG2+ BLOCKADE
NMDA receptors are unique in that they require both GLUTAMATE BINDING and POSTSYNAPTIC MEMBRANE DEPOLARISATION to function.
When the membrane is at resting potential, a magnesium ion (Mg2+) blocks the ion channel pore of the NMDA receptor. Depolarization of the membrane displaces the Mg2+ ion, allowing ions to flow through the open channel.

Question 16

disfunction of the GLUT-NMDA rec

Answer 16

contribution to human disease and loss of function

Question 17

difference between the 3- 2 Glutamate receptors
AMPA, NMDA and Kainate

Answer 17

AMPA- mediate FAST excitatory synaptic transmission in CNS
NMDA- slower than other isoforms, inv in learning and memory
Kainate- Similar to AMPA but a lesser role at synapses
linked to schizophrenia, depression and huntingtons

Question 18

RNA editing/ splicing/ transport in the AMPA rec-

Answer 18

used to 1. add subunit diversity- like allowing increased calcium ion permeability of the complex
2. synaptic plasticity- how the synapse alters the strength of the activity- strengthen or weaken
3. disease and neurological disorders- dysregulation of RNA processing in AMPA rec- linked to epilepsy and neurodegenerative disorders

Question 19

example of dysfunction of glutamate receptors- NMDA- overstimulation of NMDAR

Answer 19

= neuronal death= exitotoxicity

Question 20

How the overstimulation of the NMDAR leads to excitotoxicty= neuronal death
from Ca2+

Answer 20

increased Ca2+ influx leads to a signalling cascade ultimately leading to neuronal cell death
after the glutamate release presynaptically, then the NMDAR activation, and Calcium influx
1. intracellular signalling cascades= cascade leading to activation of enzymes like phospholipases, proteases and kinase- can damage intracell structures etc
2. mito dysfunction- distrupt mitochondrial function= decrease in ATP production and release of pro-apoptotic factors
etc

Question 21

dysfunction of RNA modification= leading to pathologic conditions
3 examples of the AMPA2 activity

Answer 21

1. downreg of GluA2 Q/R editing in motor neurones of ALS patients = increase of Ca2+ permeable AMPAR causes damage to glutamate excitotoxicity
2. In glioblastoma, decreased ADAR2 activity correlated w/ increased malignancy
   increase in Ca2+= Akt pathway promoting proliferation and tumourigenesis

Question 22

P2X receptors- trimeric
structure, binding + site

Answer 22

3 subunits w/ 2 TM helices
3 ATP molecules needed to open channel
IIII- added info, large extracellular domain- where the ATP binding is
, widely expressed, and P2X1-7 subtypes of subunits

Question 23

Importance of the P2XR’s

Answer 23

Neurotransmission- activation of P2XR in neurones > release of neurotransmitters and modulation of neuronal activity
Pain perception- in sensory neurones- lead to transmission to CNS
Immune response- on immune cells, can regulate immune cell activation, inflammation and cytokine release
Cardiovascular sys- in smooth muscle cells

Pharmacology- targets of drug development, both agonist and antagonists- been developed to modulate P2XR activity
-pain management, inflammation control etc