Session 5

Question 0

Describe some aspects of the diversity of Ca2+ channels

Answer 0

A blocker that blocks one channel may not necessarily block another, can have a localised effect.
There are different isoforms, types, blockers and primary locations.
E.g. Isoform a1C,D,S is an L-type Ca2+ channel, blocked by DHP (dihydropyridines e.g. Nifedipine) and found in all muscles, neurones, lungs.

Question 1

Outline how action potentials open Ca2+ channels on cell membranes

Answer 1

AP arrives at presynaptic membrane –> depolarisation opens voltage gated Ca2+ channels –> calcium enters –> [Ca2+]i increases –> neurotransmitter is released

Question 2

Describe events underlying fast synaptic transmission

Answer 2

In fast synaptic transmission, the receptor protein is also an ion channel. The binding of transmitter causes the channel to open.

Question 3

Describe some properties of ligand gated ion channels, with nicotinic acetylcholine receptors as an example

Answer 3

Ca2+ binds to synaptotagmin, leading to the formation of the snare complex and ACh is released through the fusion pore.
The released ACh will bind to the nicotinic ACh receptor on the post junctional membrane to produce an end-plate potential. This depolarisation will raise muscle above threshold so an AP is produced.

Question 4

Describe the action of two types of blockers of nicotinic receptors

Answer 4

Competitive blockers e.g. Tubocurarine bind at molecular recognition site for ACh
Depolarising blockers e.g. Succinylcholine cause a maintained depolarisation at the post junctional membrane - adjacent Na+ channels will not be activated due to accommodation

Question 5

Describe Myasthenia Gravis

Answer 5

An autoimmune disease where antibodies target nicotinic ACh receptors on post synaptic membranes of skeletal muscle. End plate potentials are reduced in amplitude.
Patients suffer drooping eyelids, weakness, muscle fatigue that increases on exercise.
Treatment - AChesterase inhibitors

Question 6

Discuss the importance of the control of intracellular calcium concentration

Answer 6

Many cellular processes are calcium sensitive e.g. fertilisation, secretion, neurotransmission, metabolism, contraction, learning and memory, apoptosis and necrosis.
Ca2+ can’t be metabolised so regulation is based on moving calcium into and out of the cytoplasm

Question 7

Describe the setting up and maintenance of the Ca2+ concentration gradient

Answer 7

Membrane impermeability - open/closed state of ion channels
Ca2+ATPase - high affinity, low capacity, increased [Ca2+]i, Ca2+ binds to calmodulin, calmodulin binds to Ca2+ATPase and is removed from cell,
NCX - low affinity, high capacity, Na+ gradient used as a driving force, 3Na+ in, 1Ca2+ out, antiporter is electrogenic
Ca2+ buffers - limit diffusion through ATP and Ca2+ binding proteins (parvalbumin, calreticulin, calbindin, calsequestin)
Intracellular stores

Question 8

Describe how intracellular calcium is elevated

Answer 8

Altered permeability - voltage operated calcium channels, receptor operated ion channels
Rapidly releasable stores - G protein coupled receptors (Gaq –> PIP2 –> IP3), calcium induced calcium release (Ryanodine receptor)
Non-rapidly releasable stores (microdomains, Ca2+ uniporter)

Question 9

Describe how intracellular calcium is returned to basal levels

Answer 9

Termination of signal, calcium removal, calcium store refilling (including store operated calcium channel)