Drugs & The Nervous System (l9-13)

Question 1

Name and explain the main neuronal signalling

Answer 1

1. Electrical signalling= action potential

2. Chemical signalling= neurotransmission

Question 2

Explain the resting membrane potential

Answer 2

• 2 K+ are pumped in for every 3 Na+ pumped out, so Na is concentrated outisde the cell
• Large anions are trapped within the cell. Membrane is permeable to Cl- but forced to stay outside by electrical gradient
• Membrane is partly permeable to K+ ions but forced to stay inside by Na/K ATPase and electrical gradient

Question 3

How is neurotransmission initiated and terminates?

Answer 3

• Depolarisation of neuron terminal causes Ca++ dependent exocytosis and voltage sensitive Ca++ channels open
• Vesicles fuse with presynaptic membrane and empty into synaptic cleft
• Action is terminated by high affinity reuptake which removes the transmitter from the synaptic cleft (intraneuronak metabolism inactivates transmitter)
• Metabolic enzyme can also be used for extraneuronal metabolism

Question 4

Explain the action of ligand gated ion channels receptors

Answer 4

• Receptor with binding site directly linked to an ion channel, and binding to the receptor opens the channel (via allosteric changes)
• Ions enter or cell altering membrane potential. NMDA (glutamate), Nicotinic (ACh) and 5-HT3 are Na+ (Ca++) channels excitatory, while GABAA is a Cl- channel inhibitory
• Mediates fast neurotransmission, alters membrane potential directly as Na+ depolarise

Question 5

Explain the action for G-protein Linked Receptors

Answer 5

• Receptor in which binding site is linked to a G protein
• Binding to the receptor activates enzymes, second messengers and open ion channels. Effects are slow & modulatory
• Neurotransmission presents many sites for pharmacological intervention

Question 6

Explain the storage and release of transmitters

Answer 6

• Vesicle disrupter cause an initial increase in release then a decrease
• Releasing agents cause a non-impulse dependent release
• Inhibitors of metabolic enzymes can increase the transmitter in each vesicle. Intraneuronal metabolism is inhibited

Question 7

How can the action of transmitters be terminated?

Answer 7

• a block of reuptake which causes a build-up of transmitters in the synaptic
• inhibition of metabolism which causes an increase in the lvl of transmitter in synaptic cleft

Question 8

Describe the pharmacology of acetylcholine:

Answer 8

• Synthesis: choline acetyl transferase
• Storage: vesicles
• Release: exocytosis
• Termination: in synapse by acetylcholine esterase
• Receptor interactions: muscarinic/ nicotinic which are both cholinergic receptors (receptor on surface of cells that get activated when they bind)