Lecture 14 Flashcards Preview

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Flashcards in Lecture 14 Deck (26):
1

What are the 3 methods for terminating synaptic activity?

Diffusion
Enzymatic degradation
High affinity reuptake

2

How do you test for NT receptors on a membrane?

In vitro binding assay
- Get membrane with receptor
+ radioactive NT to get amount bound vs. free

3

What is Kd?

Dissociation constant
LOW Kd = HIGH affinity

4

What are the 2 main signaling pathways at post-synaptic receptor?

Direct: receptor = channel
Indirect: receptor uses intracellular messengers to change channel permeability
GOAL of both is to affect membrane permeability

5

What is a high gain signal?

Small signal yields large downstream response
Ex: 1 NT binding --> large intracellular cascade

6

Are NT responses on/off or enduring?

BOTH
Most on/off
Some enduring:
- Repeated stimulation of receptor --> over-production of 2nd messengers
- 2nd change gene expression --> new gene product changes how the target channel responds to the receptor being activated

7

Describe how ACh is made. What is the rate limiting step

ACoA + choline --> ACh
Choline acetyltransferase = CAT
- Only found in cholinergic neurons
Rate limiting step = uptake choline from periphery

8

Where is ACh made in the neuron?

@ terminal in cytoplasm
This is where CAT is

9

How is ACh concentrated into vesicles?

H+ gradient via proton transporter

10

Describe agonist vs antagonist.

Agonist = normal NT receptor relationship
Antagonist = other molecule blocks NT binding to receptor so downstream molecules stay OFF

11

What is an ACh antagonist?

BUTX

12

Describe the ACh receptor. Where does ACh bind to it?

1 unit:
- 4 subunits = A, B, G, D
- 4 transmem domains
1 receptor = 5 units together
ACh binds the alpha unit
Na pore - lined with negative charges as selectivity filter

13

What are the 2 types of ACh receptors? Describe each.

Nicotinic @ skeletal muscle, sympathetic and parasymapthetic neurons, some brain

Muscarinic @ most brain, heart, smooth muscle, sympa neurons
- Large C term for interaction with G protein (indirect method)

14

What enzyme breaks down ACh?

Acetylcholinesterase

15

What is ACesterase's mechanism?

2 subunits
Activated serine in 1 subunit hydrolyzes ACh --> UNSTABLE acyl intermediate
Spontaneously regenerates the enzyme, choline and acetic acid

16

What are some features of ACesterase antagonists? What is the net effect?

All phosphoesters with "active ester bond"
Agonists bind ACesterase and hydrolyze the enzyme - makes it into a suicide enzyme - no longer functional
Result: ACh stays active in the synapse longer

17

What is a molecule that counters ACesterase antagonists?

PAM
Regenerates active ACesterase enzyme

18

What happens to the choline produced via ACh breakdown?

Recycled into nerve terminal to regenerate ACh

19

______ neurons are ALL cholinergic.

MOTOR

20

Which ACh neuronal pathway degenerates in Alzheimer's patients?

Start: nucleus basalis
End: various cortex

21

Are congenital issues with ACh/CAT common?

NO

22

Describe the pathology and symptoms of myasthenia gravis. Which nerves or muscle are most effected?

Pathology = make Abs against ACh receptor - acts as an antagonist
- ↓ # receptors because Ab increase turnover
Symptoms = muscle weakness with increased use, ptosis
CN and limb muscles particularly effected

23

What drug is used to treat MG patients?

ACesterase inhibitors - keep more ACh in synapse to bind to whatever functional receptors there are

24

What is Lambert-Eaton syndrome? Describe pathology and symptoms.

Pathology = Abs against pre-synaptic Ca2+ channels --> hard to get depolarization
Symptoms = weak resting muscle, strength increases with use

25

What other disease might LE syndrome be associated with?

Small cell lung cancers

26

What drug is used to treat LE patients?

K channel blocker - prevents repolarization
Prolongs depolarization