Flashcards in Session 5 Deck (29)
How does an action potential effect calcium channels?
It causes them to open as they are voltage gated so calcium enters the cell down a concentration gradient. There is an increase in intracellular calcium which causes a release of neurotransmitter.
A blocker will block one calcium channel, but not another. Why is this?
Because they are diverse and different channels can be targeted for a localised blockage.
How does calcium cause the release of Ach?
It binds to Synaptotagmin which causes a snare complex to form so Ach can be released.
What happens when Ach reaches the post synaptic membrane?
It will bind to the Nicotinic Ach receptor to produce an end plate potential. This depolarisation can raise the muscle above the threshold so that an action potential is produced.
What are the two types of blockers?
Competitive and Depolarising.
How do competitive blockers work?
They bind at the molecular recognition site for Ach. Eg Tubocurarine
How do depolarising blockers work?
Cause a maintained depolarisation at the post junctional membrane so Na+ channels will not be activated due to accommodation. Eg Succinylcholine (Used in operations to induce paralysis)
What is Myasthenia Gravis?
An autoimmune disease that targets Nicotinic Ach receptors.
What are some of the symptoms of Myasthenia Gravis?
Patients have drooping eyelids, weakness (increases with exercise)
What causes Myasthenia Gravis?
Antibodies are directed against Nicotinic Ach receptors on the post synaptic membrane of skeletal muscle. There is reduced end plate potential amplitude leading to the symptoms.
How can you treat Myasthenia Gravis?
With Ach esterase inhibitord so the amount of time Ach is in the synaptic cleft increases.
Why does the intracellular calcium concentration need to be tightly controlled?
Because many cellular processes are calcium sensitive. Because calcium cannot be metabolised the cell can only regulate it by moving calcium in and out of the cytoplasm.
What are the advantages of a large calcium gradient?
Little movement can cause changes in intracellular calcium rapidly.
What are the disadvantages of a large calcium gradient?
If a calcium overload occurs there is a loss of regulation and cell death.
What is the calcium gradient at rest?
What does the calcium gradient depend on?
Relative impermeability of the membrane
The ability to expel calcium (using Ca2+ ATPase. Na+/Ca2+ exchanger)
Intracellular Ca2+ stores (RapidlyVs non rapidly releasable)
How does Ca2+ ATPase expel Ca2+?
It is high affinity, low capacity. Intracellular Ca2+ increases and binds to calmodulin (binding trigger protein) which then binds to Ca2+ ATPase and calcium is removed.
How does Na+/Ca2+ exchanger expel Ca2+?
It is low affinity, high capacity. The Na+ gradient is a driving force and brings in 2Na+ per 1Ca2+ out.
How do Ca2+ buffers control Ca2+ levels?
They limit diffusion through ATP and Ca2+ binding proteins eg calbindin. Diffusion depends on the concentration of binding molecules and the level of saturation.
How is intracellular Ca2+ increased?
Calcium can influc across the membrane (Altered permeability)
Calcium can be released from rapidly releasable stores
Calcium can be released from non rapidly releasable stores.
How can calcium influx occur due to an altered membrane permeability?
Voltage gated calcium channels (open to allow influx of calcium down its concentration gradient triggered by membrane potential)
Receptor operated calcium channels (Ligand binds to the channel and opens it allowing calcium to enter down its concentration gradient.
How can calcium levels vary due to its release from rapidly releasable stores?
Comes from the sarcoendoplasmic reticulum;
G protein coupled receptors can trigger the release of calcium OR Calcium induced calcium release can occur - Calcium binds to Ryanodine receptors in the SER which triggers release of calcium down its concentration gradient.
What is an example of an important physiological role of calcium induced calcium release?
In the cardiac myocyte - Calcium entry through voltage gated channels following depolarisation of the membrane binds to the ryanodine receptors to cause a large release of calcium from intracellular stores.
How can mitochondria protect the cell from high calcium concentrations?
It can take calcium into it.
What are Microdomains?
Areas of cytoplasm with a higher concentration of calcium due to their proximity to a channel.
How can calcium release from non rapidly releasable stores effect calcium levels?
Mitochondria participate in normal calcium signalling and sgtimulation of ATP production. They do this using a Ca2+ uniporter that is driven using respiration.
Why is it important that calcium is returned to its basal state?
Because repetitive signalling requires a return to basal state and sustained levels of high calcium is toxic to cells.
What does a return to basal level calcium require?
Termination of signal
Calcium store refilling