Session 5 - Electrical excitability Flashcards
Why is there such a wide diversity of functions for Ca channels?
-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
Name a drug which blocks L-type calcium channels
-Dihydropyridines
Why is calcium needed in a fast-synaptic nerve terminal?
- In order to release neurotransmitter
- Depolarisation of nerve terminal-> opens voltage-gated Ca2+ channels-> influx increasing intracellular calcium->release of neurotransmitter
What happens to the membrane potential of a nerve cell when voltage-gated Ca channels open?
-Moves towards Eca
Why does the opening of Ca channels raise intracellular calcium so significantly?
- 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
What are the molecular events, inside a nerve terminal which lead to the release of neurotransmitter?
- 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
What is the relationship between the amount of Ca and the amount of neurotransitter release?
-The greater the Ca entry into the cell, the more Ach released
How does the release of Ach allow the AP to continue across the synapse?
-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
How are calcium channels opened in cell membranes by AP?
-Calcium channels are voltage gated and voltage-sensor subunit detects change in membrane potential caused by AP and changes to open configuration
The NachR channel is cation selective, in that it lets both Na+ and K+ through, so why is Na the predominant current at synapses?
- 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
Why does the AP in fast synapses never surpass -10mV?
-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
How is Ach degraded in the synaptic cleft?
-By acetylcholinesterase
What is an endplate potential?
-The initial MP response to ach, taking the membrane to depolarisation threshold for contraction
What is a miniature end plate potential?
-A miniature depolarisation, not to threshold, caused by the spontaneous release of neurotransmitter vesicles
How does a competitive NachR inhibitor work?
-Binds to Ach binding site when the receptor is closed and blocks it
How can a competitive NAchR inhibitor be overcome?
-By increasing levels of Ach
Name a competitive NAchR inhibitor
-tubocurarine
How does a depolarising blocker work?
- 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
Name a depolarising NachR blocker
-Succinylcholine
What is myasthenia gravis?
-An autoimmune disease where there is destruction of the motor end plate, resulting in the loss of NachR and profound weakness
What happens to an end plate potential at extracellular Ca decreases?
-It decreases in size
