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41 Cards in this Set

  • Front
  • Back
What are the 2 broad groups of CNS Neurotransmitters?
FAST acting - They activate LIGAND gated receptors
SLOW acting - they activate G proteins
What is another name for LIGAND gated recptors?
Ionotropic - activation leads to an influx of ions
What is another name for Gprotein recptors?
Metabotropic
Give some examples of fast acting NT that bind Ionotropic/Ligand gated receptors?
Acetylcholine
GABA
Glycine
Glutamate
Give some examples of slow acting NT that bind Metabotropic/G protein receptors?
Catecholamines -Dopamine, NE, Epi
Indolamines - 5HT
What determines whether a NT is fast or slow?
The Receptor to which the NT binds NOT the NT

e.g Ach is fast on a nicotinic recptor (ligand gated) but slow on muscarinic receptor (Gprotein)
What are the targets of activated G protein subunits?
Ion channels - activation of G proteins can modulate VOLTAGE gated ion channels
Membrane bound enzymes -interaction of G-proteins with enzymes leads to prod'n of 2nd messengers
What effect does 2nd messengers have on channels ?
They open or close Voltage gated channels
What are the 2 main target enzymes of G protein subunits?
Adenylate cyclase - catalyses formation of cAMP
Phospholipase C - catalyses formation of IP3 and DAG
Communication between neurons in the CNS occurs mainly via.....?
Chemical synapses
Recall the propagation of an action potential
1. action potential in a presynaptic neuron propagates to the synaptic terminal
2. this activates voltage gated Ca2+ channel causing calcium influx
3. the calcium promotes fusion of vessicles containing NT to the synaptic membrane
4. the NT is released into the cleft and diffuses to reach the post synaptic membrane
5. binding of the NT to the receptors cause a 'brief change in the membrane conductance of the postsynaptic neuron'
How can NTs be classed depending on the nature of the action they elicit?
Excitatory or
Inhibitory
How do Excitatory NTs (eg Glutamate) work?
They cause an Influx of Na+ ions
This results in an EPSP -Excitatory Post Synaptic Potential
The EPSP depolarizes the post synaptic neuron to threshold and
An ALL or NONE Action Potential is generated
How do Inhibitory NTs (eg GABA or Glycine) work?
They cause an Influx of Cl- ions
This results in an IPSP -Inhibitory Post Synaptic Potential
What do IPSP cause?
IPSPs cause hyperpolarization of the post synaptic neuron
It opposes the generation of an action potential
How do drugs act on the CNS to produce their effects?
By modyfying some step in the chemical synaptic transmission

They can be divided in to

Pre-synaptic
Post synaptic
Name the steps involved in the Presynaptic effect of CNS drugs.
Storage
Metobolism
Release
Uptake and Degradation
Which drugs can affect Storage of NTs?
Reserpines depletes the synapses of Monoamines (NE)

By blocking VMAT-the transporter that takes the Monoamines into the storage vessicles
Which drug affects Metabolism?
*Vigabatrin
It inhibits GABA aminotransferase that degrades GABA

*MAO Inhibitors
they inactivate the enzyme MAO allowing the NTs to accumulate and leak into the cleft
Which drug affects Release?
Amphetamines induces release of Catecholamines

(by getting uptaken via NET1 receptor in the presynaptic bouton and displacing NE from the storage vessicle)

Tyramine works the same way
How does Carbamazepine affect NT release?
They block v.gated Na+ channels - Inhibit GABA release
Which step does TCAs act?
TCAs block uptake of NE and 5HT

(same as cocaine)
What drugs affect degradation of NTs at the cleft?
Anticholinesterases block degradation of Ach
What are the 2 broad categories of the neuronal system of the CNS?
*Hierarchal
*Non-specific or Diffuse neuronal
What pathways are under the Hiearchal system?
Sensory Perception
Motor control
What are the Principal NTs of the Hierarchial system?
Excitatory: Glutamate
Inhibitory: GABA or Glycine
What functions are controlled by the Nonspecefic/diffuse neuronal system?
Global functions:
Sleeping
Walking
Attention
Appetite
Emotional States

The NTs of this system are Monoamines
Dopamine
NE
5HT
Which NTs are Amino Acids?
Glycine and GABA -NEUTRAL A.A

Glutamate and Aspartate - ACIDIDC A. A
Which group of Amino acid NTs are Inhibitory?
Neutral Amino acids- GABA and Glycine

They increase membrane permeability to Cl- ions
Where does Glycine act?
SPINAL CORD

The Glycine receptor is a Chloride channel
Which GABA receptor is G protein coupled?
GABA(b) Receptors - they are coupled to G proteins that Inhibit Ca2+ channels or Activate K+ channels

GABA(a) receptor is a Cl- channel
The Acidic amino acids work on which 2 receptor classes?
Ionotropic receptors -gated cation-selective channels
Metabotropic receptors -act indirectly on channels via G proteins
What action do both the acidic amino acids NT have on the neurons?
They are both Excitatory - Glutamate and Aspartate
What are the 3 subtypes of ionotropic receptors that acidic a.a bind to?
Kainate
AMPA
NMDA

Note: Ionotropic receptors are present at MOST Excitatory synapses in the Brain
What action do both the Acidic amino acids NT have on Metabotropic Receptors?
The Gprotein subunits:
Activate Phospholipase C (post-synaptic)
or
Inhibit Adenylyl Cyclase (Presynaptic)
Most CNS responses to Ach are mediated by which type of receptors?
G protein coupled MUSCARINIC receptors
What is the general action of Dopanine in the CNS?
INHIBITORY

Can be excitatory in some pathways
How is the action of NE and 5HT similar?
They can be both INHIBITORY or EXCITATORY
Name some peptide Nts?
Opioid peptides
Neurotensin
Substance P
Somatostatin
Cholecsytokin
Neuropeptide Y
Thyrotropin Releasing Hormone TRH

NB Pepetides often Coexist with a Conventional NT in the same neuron
What is the understood role of Nitric oxide, NO?
Vascular smooth muscle relaxation

Role is unclear in synaptic transmission or synaptic plasticity
These were not that bad!!!
Hmmm...