Cellular Response To Action Potentials Flashcards
What triggers the release of acetylcholine?
An increase in intracellular calcium concentration. This is caused by an action potential which opens voltage-gated calcium channels. Calcium binds to synaptotagmin which leads to formation of the snare complex and Ach release.
What is fast synaptic transmission?
The receptor protein is also an ion channel. Binding of transmitter causes the channel to open
Name a competitive blocker
Tubocurarine
How do competitive blockers work in acetyl choline channels?
Bind at the molecular recognition site for Ach.
How do depolarising blockers work?
Cause a maintained depolarisation at the post-junctional membrane. Adjacent sodium channels are not activated because of accommodation.
Example of a depolarising blocker and what it is used for
Succinylcholine
Induce paralysis
Pathology of myasthenia gravis?
Antibodies directed against nicotinic Ach receptors on the postsynaptic membrane of skeletal muscle. Endplate potentials are reduced in amplitude.
Symptoms of myasthenia gravis?
Drooping eyelids, profound weakness, fatigue
How is myasthenia gravis treated?
Ach-esterase inhibitors which increase the amount of time Ach is in the synaptic cleft.
Name some cellular processes which are calcium sensitive
Fertilisation Secretion Neurotransmission Metabolism Contraction Apoptosis Learning and memory Necrosis
Why does selectively blocking a calcium channel often have a local effect
Because calcium channels have structural diversity and different calcium channels have different primary locations.
Where are L-type calcium channels found?
Muscles, neurones and lungs
What can L-type calcium channels be blocked by?
Dihydropyridines such as nifedipine
What causes calcium entry into a cell to release neurotransmitter?
Depolarisation which opens voltage-gated calcium channels
Structure of a calcium channel?
Similar to a sodium channel
One polypeptide consisting of 4 homologous repeats is what makes up the pore-forming subunit
Each repeat consists of six transmembrane spanning domains
Have structural diversity
At rest, what are the intracellular and extracellular calcium concentrations?
Intra: 100nM
Extra: 1-2mM
What does the calcium gradient across the membrane rely on?
Relative impermeability of plasma membrane
Ability to expel calcium across the membrane using CaATPase and Na-Ca-exchanger
Intracellular calcium stores can be rapidly and non-rapidly releasable
Affinity and capacity of Ca-ATPase?
High affinity, low capacity
How does the Ca-ATPase work?
When concentration of calcium increases, Ca binds to calmodulin, a trigger protein.
The complex binds to Ca-ATPase and Ca is removed from the cell.
Affinity and capacity of Na-Ca-exchanger?
Low affinity and high capacity
What is moved by the Na Ca ATPase pump?
3 sodium in per 1 calcium out
What do calcium buffers do?
Limit calcium diffusion through ATP and Ca binding proteins.
What does the diffusion of calcium in the cell depend on?
The concentration of calcium buffer proteins and the level of saturation.
What channels increase the permeability of the membrane to calcium?
Voltage-gated calcium channels
Receptor-opened calcium channels
How is calcium releases from rapidly releasable stores?
GPCRs
Ligand binds to GPCR on the cell membrane, activating its G-α subunit.
This binds to the membrane phospholipid, PIP2, releasing IP3.
IP3 binds to a receptor on SR, releasing calcium down its conc gradient.
What is calcium-induced calcium release?
Calcium binds to ryanodine receptor on the SR/ER.
This releases calcium down its concentration gradient
What role do mitochondria have in controlling calcium conc in cells?
Take it up when Ca conc is high.
Aid in buffering, regulating signalling and stimulation of ATP production.
Do it via the calcium uniporter, driven by respiration.
What is a micro domain?
An area of cytoplasm with a higher than usual conc of calcium due to their proximity with the channel
Example of the important physiological role of calcium-induced calcium release?
In the cardiac myocyte
- depolarisation of the membrane
- VOCCs are activated so calcium influx
- calcium bonds to the ryanodine receptor on the SR
- explosive release of calcium from intracellular stores
- calcium can bind to troponin C causing conformational shift
- tropomyosin is moved out of the binding site on the actin filament
5 mechanisms responsible for the maintenance of the resting intracellular free calcium ion concentration?
Plasma membrane Ca-ATPase (PMCA) SERCA Na-Ca-exchange Mitochondrial Ca uptake Ca binding proteins
5 mechanisms for raising intracellular free Ca concentration
IP3 receptors Ryanodine receptors Voltage-sensitive Ca channels Na-Ca-exchange Ligand gated Ca channels
Which channels mediate excitation-contraction coupling in skeletal muscle contraction?
VOCCs
What causes calcium release in skeletal muscle contraction?
Skeletal
