Neurophys 5 Ex 1

Front 1

Inotropic receptor

Back 1

functions as a ion channel like GABA
and glutamate.

Front 2

GABA(a) does most of the inhibition in our brain. whereas
Glycine

Back 2

is in the spinal cord

Front 3

nAChR receptor (Ionotropic) recognizes

Back 3

two molecules of Ach bind to the
receptor and when it happens a gate opens up and
allows Na to come in..so excitatory receptor. This is like
the neuromuscular junction.

Front 4

nAChR is a pentamer and
Ach binds to the

Back 4

alpha subunit

Front 5

Snake (Craten?) poisons paralyzes small animals
because it blocks receptor at neuromusc junction. But
how come the snake doesnt paralyze itself? and how
come the mangooze doesnt die when it eats the snake.

Back 5

The nicotinic receptor (nAChR) of the mangooze and snake are homologous which renders immunity to the venom

Front 6

- Snake poison-> antagonizes the ACh receptor, preventing ACh from binding to ACh at the neuromuscular junction but the neuromuscular junction

Back 6

remains unaffected

Front 7

Receptors in the autonomic ganglia nAChR are different
then the ones in the neuromuscular junction in that
receptors in the autonomic ganglia conduct

Back 7

both Na and
Ca2+. Also the autonomic receptors have only alpha
and beta subunits and ACh binds at a

Front 8

alpha. There many
variations of the alpha and beta subunits and
depending on which combination you get, it dictates

Back 8

get, it dictates the
nature of the receptor

Front 9

receptor. a3B2 is the one that needs the most

Back 9

the
most Ach to have half of the channels open (EC50Ach)
and it also has the lowest conductance of ions across
the channel (cond Ps)

Front 10

a4b2 is the one that neeeds

Back 10

one that needs the
least Ach to have half of the channels open. a7 receptor
is the one with the greatest conductance.

Front 11

The fact that autonomic nAChR can conduct Ca is
particularly important for

Back 11

presynaptic nicotinic receptor
because if they're bringing calcium this can augment
the voltage depedent Ca channels

Front 12

P2x receptors is similar to the nicotinic receptors except
that it is activated by

Back 12

ATP or adenosine

Front 13

The ion that goes through the GABA receptor is

Back 13

Cl-

Front 14

what is GABA function once Cl- goes through channel

Back 14

it maintains the stability of the membrane
potential so that it makes the membrane resistant to depolarization

Front 15

- Distinct binding sites for GABA which rendered allow compounds to bind like

Back 15

benzodiazepines, barbiturates, and neurosteroids

Front 16

o Benzodiazepines (ie: Valium)= increase

Back 16

the binding affinity of the receptor for GABA

Front 17

 Valium effects

Back 17

relaxation in spinal cord, hypnotic in brainstem  overall depressant

Front 18

o Barbituates and neurosteroids increase

Back 18

Cl- conductance through the channel

Front 19

nhibition) what
would happen if we add diacepan with no GABA

Back 19

around? nothing so it is not an agonist more like an adjuvant

Front 20

o Picrotoxin is an antagonist that works by

Back 20

blocking conductance

Front 21

o Convulsants are antagonists for

Back 21

GABAAR

Front 22

Glutamate receptors fall into two categories

Back 22

1. NMDA (Na and Ca) and nonNMDA (AMPA) (Na conductance) and glutamate is agonist for both. 2. metabotropic
When glutamate acts on non NMDA receptor (AMPA
receptor) glutamate is excitatory and Na channels open
this is very quickly and most neuroexcitation happens like this

Front 23

Cells with AMPA receptors can also have NMDA
receptors so when glutamate is first delivered and
AMPA receptors open and Na comes in we sustain the activation, the voltage receptor on NMDA receptor

Back 23

NMDA kicks receptor out which balances Ca and Na

Front 24

Glycine receptor is similar to GABA except that glycine receptors are

Back 24

in the spinal column

Front 25

Glycine can not only act on its receptor
as an inhibitory but it can also act on

Back 25

can also act on NMDA receptor as
a facilitator of glutamate. Zinc can also interact on NMD

Front 26

- Mg+ is a channel antagonist that sits in the channel and blocks it ->when glutamate binds, Mg+ gets

Back 26

thrown out of the channel so conductance can occur

Front 27

- Zn+ has a mild inhibitory effect on

Back 27

glutamate receptors (also has a mild excitatory effect on glycine receptors)

Front 28

- Glycine increases conductance through

Back 28

glutamate receptors

Front 29

Seratonin (5HT) and Purinergic (ATP and Adenosine) Receptors
- Most are metabotrophic GCPR, but

Back 29

the 5HT3 and P2X are ionotropic

Front 30

Metabotropic Receptors = slow (seconds to hours) – ligand binds -> activates GCPR -> opens channel
- Diversity of receptor types, all with same basic structure

Back 30

7 transmembrane domains

Front 31

Metabotropic channels - Intrinsic GTPase activity

Back 31

(binding = activation, hydrolyzing = termination signal)

Front 32

Currently in the market most drugs are

Back 32

GPCRs drugs (Metabotropic)

Front 33

- A single NT can work through different GPCRs to have different effects (ie: 5HT works through different channels to affect

Back 33

appetite, mood, anxiety, and gut motility)

Front 34

Activation of adenylyl cyclase through

Back 34

(5HT4, 6, 7) Gs

Front 35

Inhibition of adenylyl cyclase through

Back 35

(5HT1) Gi

Front 36

Activation of Phospholipase through

Back 36

(5HT2) Gq

Front 37

Na+ channel activation through

Back 37

(5HT3)

Front 38

5HT2c still activates phospholipase but by modifying it
with RNA editing you may alter its

Back 38

for serotonin
or interaction with Gprotein

Front 39

- Phospholipase C coupled receptors activation leads to

Back 39

inositol (IP3) and diacylglycerol (DAG)
-> Gq -> phospholipase C

Front 40

o Gq -> PLC ->

Back 40

DAG, IP3 ->>> increased Ca++

Front 41

o Gs -> activation of

Back 41

Ca++ channels

Front 42

o Gbg -> inhibition of

Back 42

Ca++ channels

Front 43

Characteristics of Adenyl cyclase

Back 43

It is not an enzyme, it
is 10 enzymes, and they have different distributions
acroos the brain so thats one way we could achieve
different regulations and different molecules regulate
them.

Front 44

Adenylate cyclase common feats are that they
are all activated

Back 44

by Gs

Front 45

Some adenylate cyclase types
are regulated by Ca calmodulin (CAM) and activated.
So if we have an NMDA receptor or a nicotinic receptor
that is briinging Ca into the cell we can

Back 45

we can activate the
adenyl cyclase

Front 46

There are other adenylate cyclases
types that get inhibited by Ca so when Ca goes up
adenyl cyclase goes down and effect of NTs causing would
adenyl cyclase

Back 46

go down

Front 47

Some
adenylate cyclase is activated by the Gby..which means
if we have NE and its working through Gs to activate
adenylate cyclase and then we have a mGluR so
glutamate comes around and activates receptor which
releases Gyb and if the Gs that was elicited by NE the
glutamate which would

Back 47

potentiate it

Front 48

G proteins can act as second messengers. Muscarinic
receptor causes opening of the inwardly directed K
channel so it gives a

Back 48

relaxing effect to the heart done by
Gby associate with the channel. The point is that G
protein is a second messenger

Front 49

When Gby associate with a voltage dependent Ca
channel which would

Back 49

turn off leading to a relaxing effect
as well

Front 50

- Extracellular Ca++: in through plasma membrane through voltage gated and ligand gated channels; targets

Back 50

targets calmodulin, protein kinases, protein phosphatases, and ion channels; removed by Na/Ca exchanger and Ca pump

Front 51

- Intracellular Ca++: in ER through IP3 receptors and RYR receptors; targets other Ca binding proteins and adenylyl cyclase is

Back 51

removed by mitochondria

Front 52

- Ca/calmodulin activates both neuronal AC and cyclic nucleotide phosphodiesterase to increase or decrease

Back 52

cAMP
- cAMP dependent phosphorylation of some receptors promotes heterologous desensitization

Front 53

Second Messengers:Neuromodulation from fastest to slowest

Back 53

Channel sensitivity (voltage)
• Channel conductance
• Neurotransmitter sensitivity
• Enzyme activity
• Cytoskeleton
• Transcription
• Cross-regulation (interaction of multiple
neurotransmitters)

Front 54

receptor numbers can be changed by

Back 54

desensitizing
receptor or by presence of more or less NTs on the
neuron. Multiple affinity states refers to how the cycling
of GTP to GDP changes the affinity of the receptor for
the agonist.

Front 55

Homologous Desensitization

Back 55

- Altered by concentration of NT in cleft  changes in uptake
- Influenced by receptor phosphorylation
- Some receptors internalized and recycled or degraded

Front 56

- Receptors can be clustered so that GPCR and ionotropic receptors interact on specialized membrane domains

Back 56

lipid rafts, which are cholesterol rich structures)

Front 57

B-arrestin is involved in

Back 57

internalizing receptors which
causes long term response changes to receptor
regulation

Front 58

Regulation of ion channel function

Back 58

- Phosphorylation of receptor gate ->alters transmitter/effector sensitivity
- Phosphrylation of receptor channel -> alters rate of ion flux (conductance)
- Presynaptic modulation of voltage-sensitive calcium channels or vesicle membrane proteins ->attenuates or augments NT release

Front 59

o Attenuation of glutamate release by presynaptic glutamate receptors

Back 59

Presynaptic glutamate receptors -> Gbg -> interacts with Ca++ channel by decreasing Ca++ conductance -> less Ca++ flowing in
Gbg also directly affects the SNARE protein complex, which prevents vesicle fusion -> less glutamate released

Front 60

o ACh or NE potentiates glutamate signals:

Back 60

ACh or NE -> GCPR ->AC or DAG -> phosphorylation of the K+ channel ->keeps K+ channel closed -> keeps cell membrane depolarized -> increased glutamate release

Front 61

Neurotransmitter-mediated longer-term effects

Back 61

Changes at the gene level
Changes in synaptic form

Front 62

When stimulation frequency is low the shape of the
spine is being modified and at high frequency the
nature of the subunits of the receptor on the surface is
changed. This is res

Back 62

responsible for the mGluRs receptors
modulation of NMDAR (ionotropic)

Front 63

NE release regulation..glutamate release is attenuated
by presynaptic glutamate receptors (mGluR). It works
through

Back 63

Go, Gby inhibits voltage depedent Ca channel
(decreases glutamate release), and Gby interacts with
proteins in charge of vesicle release and inhibits
them..all this happens when there is too much
glutamate and it needs to be downregulated (feedback inhibition)

Front 64

Enkephalin-opiate receptor coupled to Go which causes Gby to interact with

Back 64

a voltage depedent Ca channel and this would lead to less substance P release.