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Flashcards in Holmes 5 Deck (19):
1

How do neurotransmitter concentrations drop? Enzyme for Ach? How is this a useful target for drugs?

-enzymatic degradation and uptake from neighboring cells
-Acetylcholinesterase (AChE) degrades ACh
-drugs treating dementia and Alzheimer target AChE
-Inhibitors of AchE like neostigmine help those with myasthenia gravis
-nerve gases like SARIN inhibit AChE
-excess Ach due to AChE block causes paralysis

2

How can acetylcholine have both excitatory and inhibitory actions?

Effects of a given neurotransmitter is dictated by the actions of its receptor, not due to any intrinsic properties of the neurotransmitter itself

3

Why is it important that both sites be occupied by ACh before activation?

Fail-safe mechanism (coincidence detector); wants to make sure there is high enough concentration

4

What is quantal size of postsynaptic current? MEPP?

Amount of current elicited by release of one vesicle
-miniature end plate potentials (MEPPs) is smallest possible depolarization induced in a muscle

5

NMJ is designed for ______ reliability, so every nerve AP results in enough transmitter release for postsynaptic AP.

In CNS, one synaptic input is _______ sufficient for postsynaptic AP.

100% reliability, almost never sufficient

6

What are agonist/antagonists of the nicotinic Ach ionotropic receptor?

agonist: acetylcholine, nicotine
antagonist: curare, hexamethonium, pancuronium

7

What is myasthenia gravis (MG)?

Lambert: acquired channelopathy of presynaptic channel

MG is postsynaptic disorder
-acquired autoimmune disorder
-causes muscle weakness (especially of eyelid)
-antibodies block nAChRs at post-synaptic junction, inhibits excitatory effect of Ach
-treated with AChE inhibitors, immunosuppressants, corticosteroids, neostigmine, etc.

-MG get progressively weaker from repeated attempts,
-Lambert get weak then strong (because of calcium buildup that eventually meets threshold)

8

How does nicotine work?

Stimulant/relaxant
-works with monoamine oxidase inhibitors in tobacco
-facilitates release of dopamine (mesolimbic reward neural pathways) which acts on NUCLEUS ACCUMBENS
-this is associated with reward (motivation), pleasure, euphoria, happiness in general

serotonin is other pathway: mood, memory, sleep

9

What are postsynaptic metabotropic receptors?

GPCRs
-in CNS, alpha1-adrenoceptors excite phospholipase C pathway -> DAG, Ca2+ -> PKC -> open ion channels (see yokomori lectures)

10

What activates alpha1-receptors? what do alpha1-adrenoceptors do? alpha2-adrenoceptors? alpha2-receptors?

alpha1-adrenoceptors: in smooth muscle of skin, skeletal muscle, etc. cause contraction

alpha1-receptors: respond to high concentrations of catecholamines. norepinephrine and epinephrine released by adrenal medulla DO NOT activate

alpha2-adrenoceptors have inhibitory fxn

alpha2-receptor act via inhibitory G protein to inhibit cAMP production

11

What are beta-adrenceptors?

Beta-adrenoceptors increase cAMP levels by activation of adenylyl cyclase using G protein
-this activates PKA to open ion channels

12

why is signal amplification important?

1 can amplify up to a million fold

13

how many neurons in CNS?

hundred billion

14

NMJ vs CNS ratio of nerve to input?

NMJ: one nerve: one muscle fiber
CNS: one nerve: up to 10000 inputs

15

other properties of CNS synapse?

-excitatory of inhibitory
-in CNS, AP only occurs when combined temporal and spatial summation of EPSPs and IPSPs produce depolarization strong enough
-in NMJ, synaptic transmission only by Ach, in CNS, many diff transmitters

16

stroke and excitotoxicity, what are the two diff types of events?

ischemic (artery in brain blocked, clot) or hemorrhagic event (bleeding in brain, burst of vessel)
-ischemic neuronal death highly contributed by GLUTAMATE EXCITOXICITY
-astrocytes can't remove glutamate and aspartate, results in prolonged glutamate over-excitation

17

what drug can we use for ischemic stroke?

tissue-type plasminogen activator (tPA), removes clot
-dangerous if hemorrhagic stroke (may break a clot that is forming to stop the bleeding)

18

what are drugs for selective serotonin reuptake inhibitors (SSRIs)

prozac, zoloft, paxil -> treats depression, anxiety, OCD
-block reuptake of serotonin

19

what are the types of synaptic connection in brain?

type I: glutamatergic (excitatory)
type II: GABA-ergic (inhibitory)