Intracellular calcium concentration Flashcards
Explain how action potentials open calcium channels in cell membranes
The action potential arrives at the presynaptic membrane. This causes the opening of VOLTAGE GATED Ca2+ channels and the subsequent influx of calcium ions down their concentration gradient.
This increase in intracellular calcium concentration causes the release of neurotransmitter
Describe the diversity of voltage gated calcium channels
They are similar to voltage gated sodium channels, however they have more diversity. This means that a blocker that acts upon one type of calcium channel may not work on another type of calcium channel. They have different primary locations so you can induce local calcium channel blocking.
How does an increase in synaptic calcium lead to an action potential in the post synaptic axon?
Calcium, from the calcium influx triggered by a change in membrane potential, binds to synaptotagmin and forms a snare complex. This snare complex makes a fusion pore and the neurotransmitter, i.e. ACh, is released through it. ACh binds to nicotinic receptors on the post synaptic membrane, inducing the influx of sodium ion and producing an end plate potential.
Explain competitive and depolarising blockers of nicotinic receptors
Competitive receptors bind and the molecular recognition site for ACh. Depolarising blockers do not block the initial action potential but prevent the repolarisation of the terminal; they maintain the Na channels in an inactive state.
Describe myasthenia gravis
Myasthenia Gravis is an autoimmune disease targeting nicotinic Ach receptors.
Patients suffer drooping eyelids, profound weakness, which increases with exercise. It is caused by antibodies directed against NAchR’s, on the postsynaptic membrane of skeletal muscle. Endplate potentials are reduced in amplitude, leading to muscle weakness and fatigue.
Treat with Ach-esterase inhibitors, to increase the amount of time Ach is in the synaptic cleft.
Why is it important to have tight control of intracellular calcium?
Many cellular processes are calcium sensitive, for example fertilisation, secretion, neurotransmission, metabolism, contraction, learning and memory, apoptosis and necrosis. As Ca2+ cannot be metabolised, the cell has to regulate intracellular Ca2+ concentration based largely on moving Ca2+ into and out of the cytoplasm.
Describe the setting up and maintenance of calcium concentrations
Calcium concentrations are normally very low in the cell and relatively higher outside the cell. The advantage is that calcium influx is rapid when required, but efflux is slow as it is very energy dependent. This puts the cell at risk of calcium overload.
The concentrations are set up through: selective permeability; efflux of calcium through CaATPase and Na/Ca exchanger; calcium buffers (e.g. calsequestrin) and calcium stores.
Outline CaATPase
Ca2+ ATPase
Considered to be high affinity, low capacity.
- Intracellular [Ca2+] Increases
- Ca2+ binds to calmodulin – a binding trigger protein
- Calmodulin-Ca2+ binds to Ca2+ ATPase
- Ca2+ is removed from cell
Outline the sodium calcium exchange
Na+/Ca2+ Exchanger
Considered to be low affinity, high capacity
- Na+ Gradient used as driving force (Na+/K+-ATPase) (M&R LO 2.3)
- Transports 3Na+ into the cell per 1Ca2+ out
- Antiporter is electrogenic
- Works best at resting membrane potential
How is intracellular calcium concentration increased?
- altered membrane permeability: Voltage Operated Calcium Channels (VOCC) and Receptor Operated Calcium Channels.
- Rapid release stores such as the ER (SERCA pump -Sarco Endoplasmic Reticulum Calcium ATPase). Can be activated through G proteins (GPCR, e.g. G-alpha-q Phospholipase C, PIP2 and IP3 - IP3 receptor on SER), or Calcium Induced Calcium Release (CICR) through the Ryanadine receptor on SER.
- Gs - cyclic AMP - Protein Kinase A
- Non-rapid stores - mitochondria and Ca uniport system
How is intracellular calcium returned to basal levels?
Repetitive signalling requires a return to the basal state. Further to this, too much Ca2+ for too long is toxic to cells.
A return to basal levels requires:
- Termination of signal
- Ca2+ Removal (Na/Ca exchanger, CaATPase)
- Ca2+ store refilling
Explain the process of conductance at the NMJ
- AP arrives and depolarises membrane
- VOCC open and calcium influx
- Ca binds to synaptotagmin
- Vesicles brought closer to the membrane
- Snare complex makes a fusion pore. Transmitter released.
- transmitter binds to receptors on post synaptic membrane. Open Na channels. AP formed.
