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Flashcards in Neurotransmission And Drug Mechanisms Deck (16)
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Dendrite to dendrite communication

Electrical
No neurotransmitter
Via gap junctions-> connexion a

1

Neurotransmitter features

Change membrane potential
Alter neurotransmitter release
Major excitatory transmitter-> glut amine-> depolarisation
Major inhibitory transmitter-> GABA-> hyper polarisation
Either stored in vesicles or synthesised on demand
Released via Ca dependent exocytosis
Termination via high affinity uptake or metabolism

2

Glutamate life cycle

Taken up in to glial cells-> converted to glutamine -> returned to neurone
If it is released as glutamate it has further excitatory effects

3

Low capacitance channels

Don't let much ion through

4

Types of CNS neurotransmitter

Amines and amino acids (glutamate)-> small organic molecules containing at least one N-> stored and released in synaptic vesicles
Peptides-> large molecules-> stored and released from secretory granules
Can have a mixture of both at one axon

5

Ligand gated ion channels

Membrane spanning
Four-five subunits that come together to form a pore
Neurotransmitter binds to various sites on extracellular region-> conformational change-> pore opens
Less specific -> Ach channels are permeable to Na and K->
Net effect to depolarise the post synaptic cell towards the threshold -> excitatory -> glutamate, nicotinic Ach, 5-HT3 -> Na or Ca channels
Net effect to hyperpolarise-> Cl channels -> GABA
Fast transmission

6

Excitatory post synaptic potential

EPSP
Transient post synaptic membrane depolarisation caused by pre synaptic release of neurotransmitter
Eg Ach and glutamate gated

7

Inhibitory post synaptic potential

Transient hyperpolarisation of the post synaptic membrane potential cause by pre synaptic release of neurotransmitter eg GABA

8

G protien coupled receptors

Slower and longer lasting with much more diverse post synaptic action
Activate other G protiens or second messengers
-> activate additional enzymes that regulate ion channel function and alter cellular metabolism
Wide spread effects-> metabotrophic

9

Auto receptors

Presynaptic receptors on the presynaptic axon that are sensitive to neurotransmitter-> commonly inhibit neurotransmitter release-> self regulation

10

Neurotransmitter reuptake transporters

May happen by simple diffusion
Reuptake via pre synaptic receptors->swap neurotransmitter for Na and Cl ->
May be enzymatically destroyed or relocated in to synaptic vesicles
Also exit in to glial cells
Or enzymatic destruction in cleft

11

Adrenoreceptors

a2 autoreceptor function
a2 agonist-> clonidine -> inhibits noradrenaline neuronal firing via a2 receptors in locus coerulus and terminal noradrenaline release
Noradrenaline-> regulation of arousal, mood pain
Agonists-> sedation, reduced anxiety
Antagonists-> increased vigilance, antidepressant, antixiognic
B-adrenoceptors-> increase cAMP formation

12

Drugs that act on ligand gated ion channels

Benzodiazepines
Barbituates-> GABA modulators
Ketamine
Phencyclidine-> NMDA antagonist
Adenstertron-> 5-HT3 antagonist
Nicotine-> nicotine agonist

13

Glutamate gated channels

3 subtypes-> AMPA, NMDA, kainate
AMPA, NMDA-> bulk of excitatory synaptic transmission
AMPA-> permeable to Na and K-> rapid and large depolarisation -> excitatory
AMPA and NMDA co exist at many synapses
NMDA-> permeable to Na and Ca -> widespread, lasting changes
-> voltage dependent -> at normal resting potential channel is blocked by Mg -> moves when membrane is depolarised

14

GABA gated ion channels

Mediates most synaptic inhibition
a subunits bind transmitter
Several other binding sites-> benzodiazepines, barbituates, steroids (outside), picrotoxin (inside)
Only cause effect when GABA is also bound
Benzodiazpines-> increase frequency of channel opening
Barbituates-> increase duration of channel opening
The more Cl let in the more inhibitory effects

15

Neurotransmitters and psychiatric disorders

Alziehmers-> Ach
Schizophrenia-> dopamine, 5-HT
Depression-> NA, 5-HT
Anxiety/OCD-> GABA, NA, 5-HT
Bipolar-> post receptor