Chemistry and physiology of the synapse Flashcards

1
Q

ACh on the heart

A

mAChR –>

G-protein –>

K+ channel –> hyperpolarisation

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2
Q

ACh on skeletal muscle

A

nAChR –>

Na+ channel –>

Depolarisation

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3
Q

Ligand gated ion channels

A

Responsible for fast transmission of information to the postsynaptic neuon

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4
Q

Ionotropic receptors

A

Opened by ligand binding rather than voltage change

Ligand= neurotransmitter

Allows influx of ions through central pore

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5
Q

Fast synaptic transmission: glutamate

A

Flux Na+

Excitatory post synaptic potential

Depolarises postsynaptic neurone

Threshold met causes action potential

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6
Q

Fast synaptic transmission: GABA

A

Flux Cl-

Inhibitory post synaptic potential

Hyperopolarises postsynaptic neurone

Inhibits neurone firing unless sufficient glutamate to counteract

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7
Q

Nicotinic

A

Most well studied ionotropic receptors

Activation by ACh causes excitation and contraction of muscle cells

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8
Q

Three types of glutamate receptors

A

NMDA

AMPA

Kainate

Names based on the agonists selective for them

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9
Q

NMDA receptors

A

Agonist: NMDA

Antagonist: APV

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10
Q

AMPA rececptors

A

Agonist: AMPA

Antagonist: CNQX

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11
Q

Kainate receptors

A

Agonist: kainic acid

Antagonist: CNQX

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12
Q

No-NMDA receptors

A

Fast opening channels permeable to Na+ and K+

Responsible for early phase of EPSP

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13
Q

NMDA receptor

A

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

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14
Q

NMDA receptors- regulation of channel opening

A

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

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15
Q

NMDA receptors and schizophrenia

A

NDMA receptors also inhibited by phencyclidine and MN801

Both bind in the open pore

Blockade produces symptoms that resemble hallucinations associated with schizophrenia

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16
Q

Glutamate excitotoxicity

A

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

17
Q

Glutamate

A

Excitatory

18
Q

GABA

A

Inhibitory

brain

19
Q

Glycine

A

Inhibitory

spinal cord and brain stem

20
Q

Nicotine

A

Excitatory at NMJ

Excitatory or modulatory in CNS

21
Q

Serotonin

A

Excitatory or modulatory

22
Q

ATP

A

Excitatory

23
Q

Metabotropic receptors

A

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

24
Q

GPCR

A

Seven transmembrane domain protein

Transmitter binds to extracellular domain

Binding triggers uncoupling of heteromeric G protein on intracellular surface

Transduces signal across cell membrane

25
G proteins
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
26
Alpha subunit
Gs- stimulates adenylyl cyclase Gi- inhibits adenylyl cyclase Gq- stimulates phospholipase C
27
Beta gamma complexes
Activate K+ channels directly Mode of action for muscarinic ACh receptors in heart and GABA receptor
28
Second messenger cascade: cAMP
Gs and Gi have opposite effects on adenylyl cyclase Stimulate or inhibit synthesis of cAMP and subsequent activation of protein kinase A
29
Second messenger cascade: PIP2
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
30
Kinases and phosphatases
Activity of many protein regulated by phosphorylation state Maintenance of phosphorylation an important level of control Kinase adds phosphate Phosphatase removes
31
Amplification of G protein signals
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
32
Presynaptic: Autoreceptors
Regulate release of transmitter by modulating its synthesis, release or reuptake e.g. phosphorylation of tryosine hydroxylase
33
Presynaptic: Heteroreceptors
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
34
Postsynaptic receptors
Change firing pattern of activity Increase or decrease rate of cell firing Long term synaptic changes
35
Metabotropic receptors
Metabotropic glutamate receptors GABA(b) receptor Muscarinic acetylcholine receptors Dopamine receptors Noradrenergic and adrenergic receptors Serotonin receptors Neuropeptide recetors
36
Enzyme linked receptors
e.g. receptor tyrosine kinases Transmembrane proteins with intrinsic tyrosine kinase activity Activated by neurotrophin binding On activation autophosphorylate
37
Other receptors in neurones
Membrane permanent signalling molecules activate intracellular signals e.g. NO