Lecture 8

Question 1

what is the selectivity of ion channel pores determined by

Answer 1

physical size

AA lining

Question 2

what is the structure of an ion channel

Answer 2

P loops between 2 TMD

on cytoplasmic side TMD closely packed creating gate

Question 3

describe voltage gated ion channels

Answer 3

4 subunits each with 6 TMD
voltage sensing domain adjacent to pore lining in each 4 alpha subunit
inactive peptides can swing in to block pore when activated
also had beta subunits in cytoplasm that add specificity

Question 4

what are three types of voltage gated channels

Answer 4

pentemeric = cyc-loop 
tetrameric = ionotropic glutamate
trimeric = P2X

Question 5

describe glutamate receptors

Answer 5

tetrameric ligand gated ion channels
very diverse
AMPA, kainate, NMDA

Question 6

what is an example of a pentameric channel

Answer 6

nAChR

5 subunits with 4TMD

Question 7

what is an example of a disease caused by mutation in nAChR

Answer 7

autosomal dominant nocturnal frontal lobe epilepsy

ADNFLE

Question 8

whats an example of what glutamate receptor signalling regulates

Answer 8

LTP induction
increases vescil release probability
increases amount of receptors and dendritic spines

Question 9

what receptor famiy is the largest

Answer 9

GPCR

Question 10

what is the structure of a GPCR

Answer 10

7 TMD
N terminus can bind to other proteins
most highly conserved area is signal transducing domain
agonist binding site nested in membrane
C terminus important site for regulation

Question 11

what is a PAR and give an example

Answer 11

GPCR receptor that is activated by proteinases

blood clot formation - thrombin cleaves of part of N terminus blocking channel

Question 12

basic principles of GPCR signalling

Answer 12

TM 5 + 6 move to reveal binding site
GDP disassociates - GTP associates
beta gamma subunits dissociate and are free to activate other effectors

Question 13

what are the key differences between monomeric and trimeric G proteins

Answer 13

monomeric - inactive form locked in GDP bound state - has to be associated with GEF
trimeric - agonist bound receptor acts like GEF promoting GDP-GTP

Question 14

what are examples of small molecule 2nd messengers

Answer 14

small soluble molecules (cAMP,GMP)
hydrophilic lipids confined to membrane
calcium ions
gases (NO)

Question 15

what is the local conc of 2nd messengers determined by

Answer 15

rate of:
production
diffusion from site of production
removal
e.g. [cAMP] is regulated by adenyl cyclase and removed by phosphodiesterase

Question 16

describe adenyl cyclase

Answer 16

12 TMD
2 subunits
10 isoforms
membrane anchored enzyme
activated by G-alpha subunit inhibited by G-alpha i

Question 17

describe beta-2-adrenoreceptor regulation of metabolism

Answer 17

stimulation of adenyl cyclase
cAMP production
activates PKA

Question 18

give examples of activating mutations of GPCRs causing disease

Answer 18

parathyroid Ca2+ sensor - hypoparathyroidism
rhodopsin - night blindness
thyroid hormone receptor - hyperthyroidism, thyroid cancer

Question 19

give examples of loss of function mutations of GPCR causing disease

Answer 19

con cell opsin - colour blindness
parathyroid Ca2+ sensor - hyperparathryoidism
rhodopsin - retinitis pigmentosum/degeneration
thyroid hormone receptor - hypothyroidism
vasopressin receptor - nephrogenic diabetes insipidus - failure to reabsorb water in kidneys

Question 20

what does G-alpha q act on

Answer 20

alpha-adrenergic amines e.g. ACh

Question 21

what are 5 processes regulated by Ca signalling

Answer 21

synaptic transmission
hormone secretion
fertilisation
muscle contraction
cytokinesis