Calcium in cellular function Flashcards
How is low calcium conc in the cel regulated? (3 ways)
- regulated ca entry
- regulated ca efflux
- regulated exchange between cytosol and stores
what are 4 routes of ca entry into cell?
- voltage gated calcium channels (VGCCs)
- ligand gated calcium channels (LGCCs)
- store-operated calcium channels (SOCCs)
- Na/Ca exchange
where are DHP CCBs located?
vascular/smooth tissue
where are non-DHP CCBs located?
cardiac tissue
Which channel do ω-conotoxins, such as ziconotide act on and how do they work?
N type VGCCs
prevent Ca entry into the presynaptic nerve terminal
inhibits ACh release
pain transmission inhibited
Verapamil moa?
- blocks Ltype VGCCs
- prevents influx of Ca2+
- prevents contractions
- depresses electrical activity in heart
nifedipine moa?
- blocks L-type VGCCs
- prevents ca influx into smooth muscle cell during depolarisation
Therapeutic effects of nifedipine?
- relaxes blood vessels (hypotensive)
- increases the supply of blood and oxygen to the heart while reducing its workload (antianginal)
What therapeutic effects does verapamil exert?
- relaxes blood vessels (hypotensive)
- increases the supply of blood and oxygen to the heart while reducing its workload (antianginal)
side effects of nifedepine?
dizziness
lightheadedness
reflex tachycardia - if BP decreases, the heart beats faster to raise it
side effects of verapamil?
abdo pain, dizziness, nausea, peripheral oedema
What is the only true LGC receptor in smooth muscle cell and what activayes it?
P2X receptor, activcated by ATP
How does excess Ca lead to excitotoxicity?
- NMDA Glutamate receptor has ↑Ca2+ permeability
- ↑ Ca2+ influx
- excess Ca2+ causes overactivation of NMDA receptor
- induces Ca-dependent proteases to induce apoptosis - EXCITOTOXICITY
- cell death
under what conditions do store-operate calcium channels (SOCs) allow ca entry?
when intracellular ca stores are depleted
they are NOT sensitive to intracellular ca conc
How does ca enter cells via SOCs?
- when intracellular ca conc is low
- STIM is recruited from ER and plasma membrane
- this activates ORAI1
- this allows ca entry from extracellular areas into cell
what is calcium extrusion?
- calcium actively pumped outwards across CSM
- ca pumped inwards from cytosol to ER/SR
How does Na/Ca exchanger (NCX) work?
- pumps 3 Na into cell, 1 Ca out of cell - causing DEPOLARISATION
- produces electrochemical Na conc gradient
- this energy allows countertransport of Ca
- Ca accumulates intracellularly
How do cardiac glycosides work and therapeutic effect?
therapeutic effect: increase contractile force of heart
moa:
inhibit Na/K pump
increased [Na]i slows Ca extrusion via NCX
raised [Na]i drive Ca extrusion into SR so the amount of Ca increased with each AP
this increases contractility of heart
indications of digoxin
- HF, Afib
What 3 factors determine intracellular calcium conc?
- Ca2+ entry
- Ca2+ extrusion
- Ca2+ exchange
Where does Ca2+ extrusion occur?
out of CSM
inwards across ER/SR