SESSION 7 LT 2 ELECTRICAL EXCITABILITY-SYNAPTIC TRANMISSION AND NMJ Flashcards
NAME THE THREE ION CHANNELS AT THE PRESYNAPTIC TERMINAL
- Vg Na+ Channel
- Vg Ca2+ Channel
- Vg K+ Channel
What is the Eq potential value for Ca2+?
ECa= +122 mv
What effect does increasing the action potentials have on the NT release?
- Several AP’s sequentially you have more NT release
- Structure of VG Ca2+ channel similar to Vg Na+ channel
Give an example of Specific blockers of L- type Ca2+ channels
Dihydropyridines- eg. NIFEDIPINE
Which has a strange mechanisms of action because the ionic form penetrates the plasma membrane
Binds to intramembranous site on L- type Ca2+ channel
Describe the structure of Vg Ca2+ Channels
- Can have more than just the alpha subunit
- Protein kinase can increase the activity eg VOCC channels in ionotropy
- Pore forming subunit necessary for a functional channel
- Other associated subunits fine-tune the properties and enable correct regulation of channel activity.
Properties of Ca2+ channels
- Vg Ca2+ channels activate and inactivate more slowly than Na+ channels
- Inactivation of Vg Ca2+ channels - is dependent of Ca2+
It is the increased intracellular Ca2+ concentration which leads to inactivation of Ca2+ channels.
TRANSMITTER RELEASE
- Ca2+ entry through Vg Ca2+ channels
- Ca2+ binds to synaptotagmin
- Vesicles brought close to the membrane
- Snare complex makes a fusion pore
- Transmitter released through this pore - binds to nACHr on postsynaptic membrane
How DOES depolarisation occurs in the muscle membrane ?
Post synaptically
- Ach = NT binds to nACHr on post junctional membrane
- Produce END PLATE POTENTIAL
- This depolarisation in turn raises muscle above the electrogenic threshold so an AP is produced in the muscle membrane
Why is there a greater driving force fo Na at the NMJ?
- NACHr- allows Na+ and K+ to move equally
The membrane potential for SKM= -90Mv closer to EK which is -75 mV/-70 mV - therefore, hardly any movement K+ - But further from ENa therefore greater driving force for Na this will cause an end plate potential in the muscle
What is transmitter release dependent upon and how does this affect the end plate potential?
- Transmitter release dependent on Ca2+ entry
Therefore if decreased external calcium concentration end plate potentials decrease in AMPLITUDE
WHAT IS THE RELATIONSHIP BETWEEN AN END-PLATE POTENTIAL AND MUSCLE ACTION POTENTIAL?
- synaptic potential spreads to adjacent part where you have Vg Na+ channels and you will have depolarisation and it will spread along the membrane fibre
- Ach binds to nACHr post junctional membrane - end plate potential raises the muscle above the electrogenic threshold —> AP in the muscle membrane
WHAT ARE THE BLOCKERS OF nACHr’s?
- Competitive blocker- Tubocurarine
- Depolarising blocker- Succinylcholine
How does d-tubocurarine work?
- Binds to ACH binding sites
- Prevents ACH from binding and opening the port
BUT Because its competitive binding therefore increase ACH concentration can overcome the d-TC block
How does succinylcholine work?
Depolarising blocker
- Maintained depolarisation
- Increased proportion of inactivated Na+ channels
- Fail to activate adjacent Na+ channels
WHAT IS MYASTHENIA GRAVIS?
- AUTOIMMUNE DISEASE
- TARGETING nACH receptors
-Patient suffers from profound weakness - Weakness increases with exercise
- Caused by antibodies directed against nACHR on post synaptic membrane of skeletal muscle
Antibodies leads to loss of functional nACHR - by complement mediated lysis and receptor degradation
End plate potentials are decreased in amplitude = muscle weakness and fatigue.