Session 5 - Electrical excitability

Question 1

Why is there such a wide diversity of functions for Ca channels?

Answer 1

-There are many different types of calcium channels (L-type-Muscle, N-type-Neurones, T-type-Heart) and different channels are present within different tissues

Question 2

Name a drug which blocks L-type calcium channels

Answer 2

-Dihydropyridines

Question 3

Why is calcium needed in a fast-synaptic nerve terminal?

Answer 3

• In order to release neurotransmitter
• Depolarisation of nerve terminal-> opens voltage-gated Ca2+ channels-> influx increasing intracellular calcium->release of neurotransmitter

Question 4

What happens to the membrane potential of a nerve cell when voltage-gated Ca channels open?

Answer 4

-Moves towards Eca

Question 5

Why does the opening of Ca channels raise intracellular calcium so significantly?

Answer 5

• There is a large gradient between the intracellular and extraellular compartments as Ca is so low within the cell
• This means there is a very large influx when the channels open

Question 6

What are the molecular events, inside a nerve terminal which lead to the release of neurotransmitter?

Answer 6

• Ca enters and binds to synaptotagmin which results in the Ach vesicle being brought to the membrane
• The neurotransmitter vesicle associates with the membrane and forms a snare complex
• The snare complex makes a fusion pore in the membrane, through which transmitter is released into the synaptic cleft

Question 7

What is the relationship between the amount of Ca and the amount of neurotransitter release?

Answer 7

-The greater the Ca entry into the cell, the more Ach released

Question 8

How does the release of Ach allow the AP to continue across the synapse?

Answer 8

-2 molecules of ach bind to two a-subunits on NachR on the post-junctional membrane which opens the intrinsic channel, through a conformational change, and allows the AP to continue

Question 9

How are calcium channels opened in cell membranes by AP?

Answer 9

-Calcium channels are voltage gated and voltage-sensor subunit detects change in membrane potential caused by AP and changes to open configuration

Question 10

The NachR channel is cation selective, in that it lets both Na+ and K+ through, so why is Na the predominant current at synapses?

Answer 10

• The MP of nerve cells is -90mV, Ek is -95mV so K= is almost at its equilibrium
• Ena is +30mV thus there is a large concentration gradient between the inside and outside of the cell resulting in a dominant Na influx

Question 11

Why does the AP in fast synapses never surpass -10mV?

Answer 11

-Because the NAchR is permeable to both Na+ and K+ it reaches an equilibrium in the conductance of the two ions, which is approximately -10mV

Question 12

How is Ach degraded in the synaptic cleft?

Answer 12

-By acetylcholinesterase

Question 13

What is an endplate potential?

Answer 13

-The initial MP response to ach, taking the membrane to depolarisation threshold for contraction

Question 14

What is a miniature end plate potential?

Answer 14

-A miniature depolarisation, not to threshold, caused by the spontaneous release of neurotransmitter vesicles

Question 15

How does a competitive NachR inhibitor work?

Answer 15

-Binds to Ach binding site when the receptor is closed and blocks it

Question 16

How can a competitive NAchR inhibitor be overcome?

Answer 16

-By increasing levels of Ach

Question 17

Name a competitive NAchR inhibitor

Answer 17

-tubocurarine

Question 18

How does a depolarising blocker work?

Answer 18

• Molecules cause receptors to open, producing a slow maintained depolarisation, however it doesnt not get broken down by AchE and the Na channels become inactive
• Depolarisation can not occur and the nictotinic channels have come desensitised

Question 19

Name a depolarising NachR blocker

Answer 19

-Succinylcholine

Question 20

What is myasthenia gravis?

Answer 20

-An autoimmune disease where there is destruction of the motor end plate, resulting in the loss of NachR and profound weakness

Question 21

What happens to an end plate potential at extracellular Ca decreases?

Answer 21

-It decreases in size