Calcium channels Flashcards
what is the concentration of calcium inside and outside the nerve terminal?
why is calcium homeostasis important?
internal ~1mM
external ~ 100nM
if levels of calcium are elevated for prolonged periods
- > can be damaging for synapse
- > evolves a calcium dependent form of neurotoxicity
what allows Ca2+ in?
what removes Ca2+ from the cell?
calcium channels
non-selective cation channels
- both can be ligand or voltage gated
calcium pump
- transports protons in
calcium exchanger
- transports Na+ in
what are the 2 important buffering organelles?
ER
- Ca2+ can go in and form stores
Mitochondria in synapse
what are genetically encoded calcium indicators called?
what are they?
how does it work?
Cameleons
GFP fused to calmodulin and M13 peptide of MLCK
Ca2+ binding to calmodulin
-> induces a conformational change
= alters emission properties
what are the features of a SNARE complex at 200nm from the Ca2+ channel?
1) lower concentration ~ 5-10uM
2) slower rises and falls
3) at equilibrium with movie buffers
- > so calcium can be mopped up
4) strongly dependent on buffers
5) calcium concentration is determined by mean activity of several neighbouring channels
what are the features of a SNARE complex at 20nm from the Ca2+ channel?
what are these known as?
1) higher conc ~ 100uM
2) quicker rises and falls
3) is not at equilibrium with mobile buffers
- > can overcome buffering activity as the Ca2+ conc is so high
4) almost independent of Ca-buffers
5) calcium conc determined by the local channel
Microdomains
what are micro domains critical to?
the fine spacial and temporal control needed to maintain fast excitatory neurotransmitter transmission
describe calcium-dependent NT release
e.g. glutamate
- action potential in bouton generated by Na+ channels opening
- depolarisation opens Ca2+ channels
- Ca2+ elevation occurs in micro domain
- Ca2+ binds to synaptotagmin causing opening of fusion pore
- glutamate passes through fusion pore and diffuses in the cleft
- opening of AMPA channel generates EPSC
how do action potentials trigger calcium influx?
what happens then?
when action potential reaches threshold
- > triggers depolarisation
- > inward Ca2+ current occurs
triggers NT release
-> EPSP
what is homosynaptic plasticity?
what are the 3 types?
the amount of NT released with each action potential is not constant
- but is a factor of the quanta
facilitation
potentiation
depression
what is facilitation?
what is potentiation?
what is depression?
progressive increase in release due to residual calcium at release site during a train of APs (short lasting)
increase following repetitive stimulation
termed PTP, long lasting, involves mitochondrial calcium buffering and release
progressive decrease in release during a train of action potentials due to decline in readily releasable vesicle pool
what are the features of voltage gated calcium channels?
mediate calcium influx in response to membrane depolarisation
couple electrical activity to neurophysiological events
e.g. NT release
members of a gene superfamily of transmembrane ion channels
e.g. voltage-gated sodium channels
complex proteins of 4-5 distinct subunits encoded by multiple genes
describe the structure of the voltage-gated calcium channel
alpha 1
= where most fundamental properties of the channel occur
auxiliary subunits
= important for trafficking, folding + overall function
describe the structure of the alpha subunit
10 genes
contains:
conduction pore
voltage sensing + gating
2nd messenger + toxin regulatory sites
4 homologous domains (I-IV), 6 membrane segments in each (S1-S6)
what do the homologous domains and membrane segments in the alpha subunit do?
3 amino acid changes in I, III, IV convert Na+ to Ca2+
S4 voltage sensor
S5-S6 pore loop determines ion conductance
