Intro to CNS Pharmacology

Question 1

What is the RMP in neurons?

Answer 1

• 60 mV

Question 2

Nernst Potentials for K, Na, Cl

Answer 2

K = -75mV 
Na = +55mV
Cl = -69mV

Question 3

What are the two types of synaptic potentials and what do they do?

Answer 3

EPSP: mem potential moves to more + values
IPSP: men potential moves to more - values

Question 4

Two mechanisms by which an EPSP can occur

Answer 4

1. Increased conductance: open ligand gated K or Na channels

2. Decreased conductance: close K leak channel

Question 5

Three mechanisms for production of IPSPs

Answer 5

1. Increased conductance of mem K or Cl
2. Ligand-gated Cl channel (GABA receptor)
3. GPCR can open K channel: direct interactions or by changes in phosphorylation state of K channels that are closed

Question 6

What is Norepinephrine synthesized from?

Answer 6

Tyrosine

Question 7

Where are noradrenergic neurons located?

Answer 7

Medulla oblongata, pons and midbrain = reticular activating system –> role in arousal and ANS regulation

Question 8

What is the rate limiting step/enzyme for Norepi synthesis? And what is a necessary cofactor?

Answer 8

Tyrosine hydroxylase; BH4

Question 9

Where is Norepi stored?

Answer 9

1. Vesicular; with dopamine B-hydroxylase enzyme

2. Vesicular transporters: VMATs - VMAT2 in brain

Question 10

How is Norepi released?

Answer 10

1. Ca dependent exocytosis
2. Plasma mem transporters working in reverse
3. Dendritic release: not Ca dependent

Question 11

What are the two modulating autoreceptors for Norepi release?

Answer 11

1. alpha2 receptor: inhibits release, feedback regulation

2. beta receptor: increases release, feed forward regulation

Question 12

How can Norepi be inactivated?

Answer 12

1. Diffusion
2. Neuronal reuptake – SERT, Na symporter
3. 2 catabolic enzymes: MAO, COMT

Question 13

Receptors for Norepi

Answer 13

All are GPCRs and can also bind epi

1. alpha1: non neuronal cells in periphery, coupled to 2nd messengers that increase Ca
2. alpha2: inhibits adenyl cyclase; often on presynaptic neurons; release-inhibiting auto receptor
3. beta: increases adenylyl cyclase activity

Question 14

Where is neurotensin located? What other ntm is it co-localized with?

Answer 14

Prefrontal cortex, hypothalamus and midbrain; always co-localized with dopamine

Question 15

How is neurotensin synthesized?

Answer 15

170 aa precursor –> hydrophobic signal sequence directs the protein to the ER –> packaged into secretory vesicles in the golgi (peptidases) –> processed by peptidases into neurotensin and neuromedin N

Question 16

How is neurotensin inactivated?

Answer 16

1. Non-selective peptidases
2. Diffusion
   NO reuptake but receptor can be internalized with the peptide