Pharmacology of the Nervous System

Question 1

Definition of Action Potential

Answer 1

Impulse of electrical activity that passes along neuron enabling communication within the nervous system. e.g Stimulus caused by NT binding ligand channel sodium moving through.

Question 2

AP Stage 1

Answer 2

Resting membrane potential -70mV. Stimulus causes rapid but small increase which reaches Vm threshold (-55mV). Na+ and K+ channels open (voltage gated).

Question 3

AP Stage 2

Answer 3

Depolarization of membrane caused by Na+ entering. (+30 - 40 mV reached.

Question 4

AP Stage 3

Answer 4

Na+ close, K+ channels still open, K+ continues to leave, repolarizing cell membrane (mV falling to resting)

Question 5

AP Stage 4

Answer 5

Hyperpolarization beyond resting level as K+ channels close slowly. Returns to resting as they close fully. Na+/K+ ATPase restores normal ion levels.

Question 6

What blocks conduction of APs along nerves?

Answer 6

Local anaesthetics e.g cocaine, lidocaine (-caine suffix)

Question 7

Calcium in synaptic terminal

Answer 7

AP in synaptic terminal causes Ca2+ channels to open.
Causes vesicles to fuse to presynaptic membrane and thus NT diffusing across into synaptic cleft to engage receptors

Question 8

Neurotransmitter Criteria

Answer 8

1. Present in the synaptic terminal.
2. Stored in vesicles.
3. Released in Ca2+ dependant manner.
4. Post synaptic effect (receptors on postsynaptic terminal).
5. Mechanism for termination of effect

Question 9

Excitatory vs Inhibitory NTs

Answer 9

Excitatory = glutamate, ion channels allow cations through Na+, Ca2+
Inhibitory = glycine and GABA, allow anions through Cl-

Question 10

Glutamate Synthesis (1)

Answer 10

Produced from glutamine by glutaminase.
Also from a-ketoglutarate (Kreb’s Cycle).

Question 11

Glutamate Vesicle Storage (2)

Answer 11

Vesicular glutamate transporters (VGLUTs) package into synaptic vesicles.

Question 12

Glutamate Postsynaptic Receptors (4)

Answer 12

Ionotropic - AMPA, NDMA, Kainate.
Also has metabotropic.

Question 13

Glutamate Termination Mechanism (5)

Answer 13

Excitatory amino acid transporters (EAATs) remove from synaptic. On neurons and glial cells.

Glial cells convert to glutamine export back to neuron.

Question 14

GABA Synthesis (1)

Answer 14

Synthesised from glutamate by glutamate decarboxylase, with co factor pyridoxal phosphate. (Glutamate nerves do not have this enzyme)

Question 15

GABA Vesicle Storage (2)

Answer 15

Vesicular inhibitory amino acid transporter (VIAAT) packages GABA into synaptic vesicles.

Question 16

GABA Postsynaptic Receptors (4)

Answer 16

Ionotropic - GABAa
Metabotropic - GABAb (Ga(i) GPCR)

Question 17

GABA Termination (5)

Answer 17

GABA transporters (GATs) on neurons and glial cells remove.

In glial cells metabolised by GABA transaminase into succinate (for KREBS)

Question 18

Areas in brain ACh is synthesized?

Answer 18

Basal fore brain nuclei:
- medial septal nucleus
- diagonal band of broca
- nucleus basalis
Brain stem cholinergic:
- pedunculopontine nucleus
- laterodorsal tegmental nucleus

Question 19

ACh Synthesis (1)

Answer 19

Synthesised from acetyl-coA and choline, by choline acetyltransferase (ChAT)

Question 20

ACh Vesicle Storage (2)

Answer 20

Vesicular acetylcholine transporters (VAChT) packages into vesicles.

Question 21

ACh Postsynaptic Receptors (4)

Answer 21

Ionotropic - nicotinic
Metabotropic - muscarinic (5 subtypes, GPCRs different actions)

Question 22

ACh Termination (5)

Answer 22

Broken down in synaptic cleft by acetylcholinesterase (AChE) into acetate and choline.
Reuptake into neurone by choline transporter.

Question 23

Dopamine production areas?

Answer 23

Substantia nigra - movement
Ventral tegmental area - reward and addition

Question 24

Dopamine pathways

Answer 24

Mesocortical - attention, emotional reg.
Mesolimbic - reward, motivation.
Nigrostriatal - reg. voluntary movement.
Tuberoinfundibular - hormone secretion (prolactin)

Question 25

Dopamine Synthesis (1)

Answer 25

Tyrosine to L-DOPA by tyrosine hydroxylase. L-DOPA to dopamine by dopa decarboxylase.

Question 26

Dopamine Vesicle Storage (2)

Answer 26

Vesicular monoamine transporter 2 (VMAT2) packages into vesicles.

Question 27

Dopamine Termination (5)

Answer 27

Dopamine transporter (DAT) takes up into neurons and glial cells. In glial monoamine oxidase (MAO) metabolises into DOPAC. Catechol-o-methyltransferase (COMT) breaks it down into homovanillic acid (HVA).

Question 28

Noradrenaline production, function?

Answer 28

Locus coeruleus (pons) produces but extends throughout brain. CNS- wakefulness, attention ANS- sympathetic nervous system (fight or flight)

Question 29

Noradrenaline Synthesis (1)

Answer 29

Synthesised from dopamine by dopamine-b-hydroxylase. [Remember dopamine steps][Dopaminergic neurons do not have this enzyme]

Question 30

Noradrenaline Vesicle Storage (2)

Answer 30

Vesicular monoamine transporter 2 (VMAT2) packages into vesicles.

Question 31

Noradrenaline Postsynaptic Receptors (4)

Answer 31

Metabotropic, GPCRs 2 alpha, 3 beta.

Question 32

Noradrenaline Termination (5)

Answer 32

Noradrenaline transporters (NET) into neurone or glial cells. Glial cells metabolization by MAO and COMT into vanillylmandelic acid.

Question 33

Serotonin production, function?

Answer 33

Raphe nuclei, projects through brain and spinal cord. Mood, pain, appetite, learning / memory, sleep/wakefulness.

Question 34

Serotonin Synthesis (1)

Answer 34

L-tryptophan to 5-hydroxytryptophan by tryptophan hydroxylase., 5-hydroxytryptophan to 5 hydroxytryptamine by tryptophan decarboxylase (same as dopa decarboxylase)

Question 35

Serotonin Vesicle Storage (2)

Answer 35

Vesicular monoamine transporter 2 (VMAT2) packages into vesicles.

Question 36

Serotonin Postsynaptic Receptors (4)

Answer 36

5-HT receptors all metabotropic apart from 5-HT3

Question 37

Serotonin Termination (5)

Answer 37

Reuptake by serotonin reuptake transporter (SERT), recycled repackaged. MAO also metabolises it to 5-hydroxy-indoleacetic acid.