Lecture 8 Flashcards Preview

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Flashcards in Lecture 8 Deck (21)
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1

what is the selectivity of ion channel pores determined by

physical size
AA lining

2

what is the structure of an ion channel

P loops between 2 TMD
on cytoplasmic side TMD closely packed creating gate

3

describe voltage gated ion channels

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

4

what are three types of voltage gated channels

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

5

describe glutamate receptors

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

6

what is an example of a pentameric channel

nAChR
5 subunits with 4TMD

7

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

autosomal dominant nocturnal frontal lobe epilepsy
ADNFLE

8

whats an example of what glutamate receptor signalling regulates

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

9

what receptor famiy is the largest

GPCR

10

what is the structure of a GPCR

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

11

what is a PAR and give an example

GPCR receptor that is activated by proteinases
blood clot formation - thrombin cleaves of part of N terminus blocking channel

12

basic principles of GPCR signalling

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

13

what are the key differences between monomeric and trimeric G proteins

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

14

what are examples of small molecule 2nd messengers

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

15

what is the local conc of 2nd messengers determined by

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

16

describe adenyl cyclase

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

17

describe beta-2-adrenoreceptor regulation of metabolism

stimulation of adenyl cyclase
cAMP production
activates PKA

18

give examples of activating mutations of GPCRs causing disease

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

19

give examples of loss of function mutations of GPCR causing disease

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

20

what does G-alpha q act on

alpha-adrenergic amines e.g. ACh

21

what are 5 processes regulated by Ca signalling

synaptic transmission
hormone secretion
fertilisation
muscle contraction
cytokinesis