Flashcards in Intro to CNS Pharmacology Deck (16):
What is the RMP in neurons?
- 60 mV
Nernst Potentials for K, Na, Cl
K = -75mV
Na = +55mV
Cl = -69mV
What are the two types of synaptic potentials and what do they do?
EPSP: mem potential moves to more + values
IPSP: men potential moves to more - values
Two mechanisms by which an EPSP can occur
1. Increased conductance: open ligand gated K or Na channels
2. Decreased conductance: close K leak channel
Three mechanisms for production of IPSPs
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
What is Norepinephrine synthesized from?
Where are noradrenergic neurons located?
Medulla oblongata, pons and midbrain = reticular activating system --> role in arousal and ANS regulation
What is the rate limiting step/enzyme for Norepi synthesis? And what is a necessary cofactor?
Tyrosine hydroxylase; BH4
Where is Norepi stored?
1. Vesicular; with dopamine B-hydroxylase enzyme
2. Vesicular transporters: VMATs - VMAT2 in brain
How is Norepi released?
1. Ca dependent exocytosis
2. Plasma mem transporters working in reverse
3. Dendritic release: not Ca dependent
What are the two modulating autoreceptors for Norepi release?
1. alpha2 receptor: inhibits release, feedback regulation
2. beta receptor: increases release, feed forward regulation
How can Norepi be inactivated?
2. Neuronal reuptake -- SERT, Na symporter
3. 2 catabolic enzymes: MAO, COMT
Receptors for Norepi
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
Where is neurotensin located? What other ntm is it co-localized with?
Prefrontal cortex, hypothalamus and midbrain; always co-localized with dopamine
How is neurotensin synthesized?
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