Lecture 5 - Effects of Electrical Signals, Ligand Gated Channels and Control of Intracellular Calcium Concentration

Question 1

how does an ap open Ca channels?

Answer 1

ap arrives at presynaptic membrane
opens voltage gated Ca channels
influx of Ca causes neurotransmitter release

Question 2

what does structural diversity mean?

Answer 2

a blocker that blocks one channel won’t necessarily block another

Question 3

how does Ca cause acetylcholine release?

Answer 3

Ca binds to synaptotagmin
formation of snare complex
acetylcholine release

Question 4

how does ACh transmit the ap?

Answer 4

binds to nicotinic receptor on post synaptic membrane
produces end plate potential
depolarisation raises muscle above threshold
ap produced

Question 5

what are the two types of blockers of nicotinic receptors?

Answer 5

competitive blocker

depolarising blocker

Question 6

what is a competitive blocker?

Answer 6

binds to molecular recognition site for ACh

Question 7

what is a depolarising blocker?

Answer 7

cause a maintained depolarisation at the post synaptic membrane so adjacent Na channels won’t be activated due to accommodation

Question 8

what are symptoms of myasthenia gravis?

Answer 8

drooping eyelids
profound weakness
sudden falling

Question 9

what is myasthenia gravis?

Answer 9

autoimmune destruction of ACh receptors

Question 10

what happens in myasthenia gravis?

Answer 10

endplate potentials are reduced in amplitude leading to muscle weakness and fatigue

Question 11

how is myasthenia gravis treated?

Answer 11

acetylcholinesterase inhibitors

Question 12

what are the intracellular and extracellular concentrations of Ca?

Answer 12

extracellular: 1-2mM (10-3 M)
intracellular: 100nM (10-7 M)

Question 13

what does the Ca gradient rely on?

Answer 13

impermeability of plasma membraneability to expel Ca across the membrane using Ca ATPase and ncxCa buffersintracellular Ca stored - rapidly and non rapidly releasable

Question 14

what is the role of Ca ATPase?

Answer 14

when intracellular Ca increases, Ca binds to calmodulin
the complex binds to Ca ATPase and is removed
high affinity, low capacity

Question 15

how do Ca buffers work?

Answer 15

limit diffusion through ATP and Ca binding proteins

Question 16

what are examples of Ca binding proteins?

Answer 16

parvalbumin
calreticulin
calbindin
calsequestrin

Question 17

how does altered membrane permeability increase Ca influx?

Answer 17

voltage gated calcium channels open to allow influx down concentration gradient - triggered by depolarisation
receptor operated Ca channels - ligand binds to the channel, opening it and allowing Ca to enter down concentration gradient

Question 18

how is calcium released from rapidly releasable stores?

Answer 18

gpcr - ligand binds and activates the G alpha q subunit which binds to PIP2, releasing IP3 which binds to its receptor, triggering the release of Ca down its concentration gradient
cicr - Ca binds to ryanodine receptor on SR/ER triggering release of Ca down concentration gradient - important in cardiac myocyte

Question 19

how is calcium released from non rapdly releasable stored?

Answer 19

Ca is taken into mitochondria when intracellular concentration is high
mitochondria take part in normal Ca signalling due to microdomains

Question 20

how is intracellular Ca returned to basal levels?

Answer 20

termination of signal
Ca removal
Ca store refilling by recycling of cytosolic Ca and using mitochondrial stores to replenish SR via store operated Ca channel (soc)