The NMJ From a Pharmacological Perspective Flashcards Preview

MSS - MSK Exam 3 > The NMJ From a Pharmacological Perspective > Flashcards

Flashcards in The NMJ From a Pharmacological Perspective Deck (60):
1

what to know?

put out notes packet** read it

2

junctional transmission

cholinergic > bc ACh is neurotransmitter

3

4 important steps in junctional transmission

synthesis of ACh
storage
release
degradation

*every neurotransmitter undergoes this process

4

4 steps in NMJ neurotransmission?

axonal conduction
junctional transmission
ACh signaling
muscle contraction

5

when does junctional transmission occur?

when axonal signal reaches terminal

6

what is activated by ACh?

nAChR

nicotinic acetylcholine receptors

7

choline transporter

membrane channel transports choline into cell
choline is precursor to ACh

cotransport of Na+ and choline into cell

8

choline acetyltransferase

ChAT
enzyme that combines acetyl CoA and choline to form ACh

9

hemicholinium

blocks the choline transporter

**don't need to know - bc its used in labs, not clinically

10

patients with alzheimers?

reduced cerebral production of ChAT
-therefore have less formation of ACh

11

therapy for alzheimers?

to increase ACh levels**
-to make up for loss of low levels

12

ACh vesicular transporter

shuttles ACh into storage vesicle
**requires ATP

1-5K ACh per vesicle

motor nerve terminal may have over 300K vesicles

13

voltage-gated Ca2+ channels

open with depolarization and allow Ca2+ entry into cell

promote vesicle membrane fusion

14

VAMP and SNAPs

vesicular and membrane proteins that initiate vesicle-plasma membrane fusion and release of ACh

15

how many vesicles fuse per AP?

approximately 125 vesicles

16

VAMP

vesicle associated membrane protein

17

SNAP

synaptosome associated proteins

18

what are components of SNARE complex

VAMP-SNAP

19

what does botulinum do?

cleaves the SNARE complex so you can't have vesicle fusion and ACh release

paralyzes muscles**

20

how long for fusion?

matter of milliseconds

21

acetylcholinesterase

AChE
enzyme that cleaves ACh
-into acetate and choline

22

choline transporter

recycles choline back into motor neuron

23

endocytosis?

occurs at nerve terminal to replenish the number of available vesicles

24

two sets of receptors for ACh?

nicotinic and muscarinic

25

nAChR

nicotinic ACh receptor
-also activate by nicotine

ligand gated ion channels (FAST)
sodium to flow into cell
-found pre and post junctionally

causes muscle AP and muscle contraction

26

mAChR

muscarinic ACh receptor
-also activated by muscarine
-found pre and post junctionally

G-protein coupled receptors (SLOW)
NOT located at skeletal NMJ**

27

nAChR distribution

skeletal muscle
cause contraction
respond to ACh and nicotine

28

mAChR distribution

smooth muscle
cause contraction
respond to ACh and muscarine

in cardiac muscle (SA and AV node)
-also on atrium and ventricle
-decreased HR, conduction velocity, contraction

29

subtypes of mAChR

5 in mammals M1-M5

activation is metabotropic

30

metabotropic

causes second messenger pathway

31

ionotropic

nAChR type
-ligand gated ion channel
-allows ions to pass through the channel pore
-in this case, sodium ions**

32

structure of nAChR

four-five distinct subunits

ACh binding occurs between alpha and adjacent subunit

requires binding of two ACh

subunits different depending on location of receptor
**allows for specific targeting in body of drugs

33

subtypes of nAChR

skeletal muscle Nm

peripheral neuronal Nn
central neuronal

34

skeletal muscle Nm subtype

at NMJ
excitatory > contraction
increased cation permeability

antagonists:
atracurium
vecuronium
d-tubocurarine
pancuronium

35

succinyl choline

causes very fast paralysis

even though its an agonist of Nm AChR, its acts as an antagonists

-tires out the receptors

36

what allows for specificity?

different subunit make up

37

what passes through nAChR channel?

sodium, potassium, calcium ???

sodium is main mover, which depolarizes and initiates an AP

38

prejunctional activation?

nAChR help to mobilize more vesicles
-physiological role confusing

on the presynaptic membrane***

mAChR activation results in ACh-mediated inhibition of further ACh release

39

tetrodotoxin

inhibits voltage gated Na+ channels and prevents axonal conduction in motor neuron

no AP down neuron - paralysis

40

local anesthetics

inhibits voltage-gated Na+ channels prevent axonal conduction

41

diaphragm

skeletal muscle

42

batrachotoxin

causes an increase in permeability of Na+ channels and induces a persistent depolarization
-one of the most potent toxins

43

botulinum toxin

cleaves components of SNARE
-VAMP and SNAP proteins

stop vesicular fusion

44

curare alkaloids

non-depolarizing competitive nAChR antagonist

45

succinylcholine

depolarizing nAChR agonist

only acts on the Nm (skeletal muscle) nAChR

-but acts as antagonist (tires out receptor)

46

neuromuscular blocking drugs

used for causing muscle paralysis during anesthesia induction

curare and succinylcholine

47

cholinesterase inhibitor

increase concentration of ACh at NMJ

organophosphates
-activate smooth and skeletal muscles

used in lower concentration therapeutically

48

therapeutic use of low concentration cholinesterase inhibitor?

dementia, alzheimers, parkinsons, myasthenia gravis, reversal of neuromuscular blockade during anesthesia

49

myasthenia gravis

decreased in nAChR on surface of cell

-cholinesterase inhibitor will increase ACh to activate the decreased nAChR

50

tetrodotoxin

also affects sodium channels on muscle cells (inhibits APs)

51

dantrolene

inhibits ryanodine receptor in SR
-blocks release of Ca2+
-no contraction

52

clinical use of dantrolene?

malignant hyperthermia, spasticity with upper motor neurons

53

uptake of choline

rate limiting step

54

endoytosis of vesicles

facilitated by clathrin

55

tertodotixin

puffer fish toxin

blocks axonal conduction
-blocks Na+ channels (not used clinically)

56

local anesthetics

block neuronal conduction
-inhibits Na+ channels

used for pain control during variety of clinical procedures

57

botulinum

cleaves components of core SNARE complex
-prevents ACh release

treatments:
-strabismus
-blepharosmam with dystonia
-cervical dystonia
-wrinkles of face
-

58

curare alkaloids

non-depolarizing competitive nAChR antagonist

during anesthesia to relax skeletal muscle

59

succinylcholine

neuromuscular blocking drug

binds to nAChR - acts as an agonust
-continued depolarization leads to receptor blockade and paralysis

60

dantroleine

inhibits ryanodine receptors in SR
-blocks Ca2+ release

malignant hyperthermia
spasticity with upper motor neurons
-spinal cord unjury, stroke, cerebral palsy, MS