lecture 19 redone Flashcards
heterogeneity
each component can have multiple isoforms e.g different isoforms of IP3 and RyR receptors
2 types of remodelling
phenotypic remodelling
genotypic remodelling
phenotypic remodelling
when a component becomes phosphorylates
alters transcription rate so more/less of it is produced
genotypic remodelling
mutation in the gene that is encoding to isoforms and alters the activity
phenotypic remodlling in the heart:
adrenaline binds to its receptor in the heart cells it elevates
cAMP
cAMP causes phosphorylation of
calcium signalling components (voltage operated calcium channel and SERCA), causes larger calcium transient - stronger heart contraction
phenotypic remodelling in the liver:
if liver gets damages it will down regulate
key calcium signalling components
lower frequency calcium spikes of greater duration
has lower numbers of vasopressin receptors and IP3Rs whilst the liver regenerates
phenotypic and genotypic remodelling can be negative though and causes disease e.g.
alzheimers disease (phenotypic) brodys disease (genotypic)
alzheimers disease
beta-amyloid oligomers increase calcium entry via the
NMDA receptor
also the amyloid precursor protein (APP) intracellular domain (AICD) which
increases calcium release from stores
amyloid precursor protein is in the membrane and in AD the Abeta monomers come together into oligomer and the oligomer binds to the
NMDA receptor
the oligomer binding to the NMDA receptors allows
more calcium to enter the cell
the AICD on the precursor protein gets chopped off into the cytosol and enters nucleus where it is a
transcription factor
the AICD increases the transcription of the
RyRs