Chemistry and physiology of the synapse

Question 1

ACh on the heart

Answer 1

mAChR –>

G-protein –>

K+ channel –> hyperpolarisation

Question 2

ACh on skeletal muscle

Answer 2

nAChR –>

Na+ channel –>

Depolarisation

Question 3

Ligand gated ion channels

Answer 3

Responsible for fast transmission of information to the postsynaptic neuon

Question 4

Ionotropic receptors

Answer 4

Opened by ligand binding rather than voltage change

Ligand= neurotransmitter

Allows influx of ions through central pore

Question 5

Fast synaptic transmission: glutamate

Answer 5

Flux Na+

Excitatory post synaptic potential

Depolarises postsynaptic neurone

Threshold met causes action potential

Question 6

Fast synaptic transmission: GABA

Answer 6

Flux Cl-

Inhibitory post synaptic potential

Hyperopolarises postsynaptic neurone

Inhibits neurone firing unless sufficient glutamate to counteract

Question 7

Nicotinic

Answer 7

Most well studied ionotropic receptors

Activation by ACh causes excitation and contraction of muscle cells

Question 8

Three types of glutamate receptors

Answer 8

NMDA

AMPA

Kainate

Names based on the agonists selective for them

Question 9

NMDA receptors

Answer 9

Agonist: NMDA

Antagonist: APV

Question 10

AMPA rececptors

Answer 10

Agonist: AMPA

Antagonist: CNQX

Question 11

Kainate receptors

Answer 11

Agonist: kainic acid

Antagonist: CNQX

Question 12

No-NMDA receptors

Answer 12

Fast opening channels permeable to Na+ and K+

Responsible for early phase of EPSP

Question 13

NMDA receptor

Answer 13

Slow opening channel permeable to Ca2+, Na+ and K+

Requires extracellular glycine as cofactor to open the channel

Gated by membrane voltage

• Mg2+ plugs pore at resting potential
• membrane depolarises so Mg2+ ejected allowing conductance

Responsible for late phase ESPS

Question 14

NMDA receptors- regulation of channel opening

Answer 14

Influx of Ca2+ as well as Na+ leads to activation of a number of enzymes and other cellular events

Cause widespread changes to postsynaptic cell

Action of NDMA receptors and resultant neuroplasticity may be molecular mechanisms that leads to long term memory formation

Question 15

NMDA receptors and schizophrenia

Answer 15

NDMA receptors also inhibited by phencyclidine and MN801

Both bind in the open pore

Blockade produces symptoms that resemble hallucinations associated with schizophrenia

Question 16

Glutamate excitotoxicity

Answer 16

Excessive Ca2+ influx into cell activates calcium dependent enzymes that degrade proteins, lipids and nucleic acids

Occurs after cardiac arrest, stroke, oxygen deficiency and repeated intense seizures

Question 17

Glutamate

Answer 17

Excitatory

Question 18

GABA

Answer 18

Inhibitory

brain

Question 19

Glycine

Answer 19

Inhibitory

spinal cord and brain stem

Question 20

Nicotine

Answer 20

Excitatory at NMJ

Excitatory or modulatory in CNS

Question 21

Serotonin

Answer 21

Excitatory or modulatory

Question 22

ATP

Answer 22

Excitatory

Question 23

Metabotropic receptors

Answer 23

Transduce signals into cell not directly though an ion channel but through G-protein which triggers series of intracellular events

Question 24

GPCR

Answer 24

Seven transmembrane domain protein

Transmitter binds to extracellular domain

Binding triggers uncoupling of heteromeric G protein on intracellular surface

Transduces signal across cell membrane

Question 25

G proteins

Answer 25

1. In resting state heteromer bound to GDP
2. On binding of ligand to receptor, GDP switched for GTP and heteromer splits
3. Ga subunit and GBy divide and diffuse separately through membrane
4. Stimulate activities of other effector proteins

Question 26

Alpha subunit

Answer 26

Gs- stimulates adenylyl cyclase

Gi- inhibits adenylyl cyclase

Gq- stimulates phospholipase C

Question 27

Beta gamma complexes

Answer 27

Activate K+ channels directly

Mode of action for muscarinic ACh receptors in heart and GABA receptor

Question 28

Second messenger cascade: cAMP

Answer 28

Gs and Gi have opposite effects on adenylyl cyclase

Stimulate or inhibit synthesis of cAMP and subsequent activation of protein kinase A

Question 29

Second messenger cascade: PIP2

Answer 29

Gq activates phospholipase C

Converts PIP2 to IP3 and DAG

DAG activates protein kinase C and IP3 releases Ca2+ from internal stores

Activates Ca2+ dependent enzymes

Question 30

Kinases and phosphatases

Answer 30

Activity of many protein regulated by phosphorylation state

Maintenance of phosphorylation an important level of control

Kinase adds phosphate

Phosphatase removes

Question 31

Amplification of G protein signals

Answer 31

G protein signalling provides method of amplifying signals between neurones

One transmitter bound to receptor can uncouple multiple G-protein heteromers

Signal can be amplified at every stage

Weak signal at synapse can cause amplified response in postsynaptic cell

Question 32

Presynaptic: Autoreceptors

Answer 32

Regulate release of transmitter by modulating its synthesis, release or reuptake

e.g. phosphorylation of tryosine hydroxylase

Question 33

Presynaptic: Heteroreceptors

Answer 33

Regulate synthesis and/ or release of transmitters other than their own ligand

e.e. NE can influence release of ACh by modulating a-adrenergic receptors

Question 34

Postsynaptic receptors

Answer 34

Change firing pattern of activity

Increase or decrease rate of cell firing

Long term synaptic changes

Question 35

Metabotropic receptors

Answer 35

Metabotropic glutamate receptors

GABA(b) receptor

Muscarinic acetylcholine receptors

Dopamine receptors

Noradrenergic and adrenergic receptors

Serotonin receptors

Neuropeptide recetors

Question 36

Enzyme linked receptors

Answer 36

e.g. receptor tyrosine kinases

Transmembrane proteins with intrinsic tyrosine kinase activity

Activated by neurotrophin binding

On activation autophosphorylate

Question 37

Other receptors in neurones

Answer 37

Membrane permanent signalling molecules activate intracellular signals

e.g. NO