Transmitters

• RECEPTORS

  • binds an information-carrying molecule (agonist)
  • passes on the information in a different form --> transfusion
  • changes cell behaviour 
  • eg. nicotinic acetylcholine receptor
  • 4 main type of receptors

  1. ligand-gated ion channel (nicotinic acetylcholine receptors + ionotropic and cys loop receptors)
  2. g-protein coupled receptors (metatropic receptors)
  3. receptor tyrosine kinase
  4. nuclear hormone receptor
• RECEPTOR TRYOSINE RECEPTORS

  • membrane bound
  • when activated --> signal is sent through the membrane and triggers protein kinase activity
  • phosphorylation --> drastically changes behaviour
• NUCLEAR HORMONE RECEPTOR

  • intracellular
  • bind agonist that have to cross the cell membrane
  • interact with specific segments of DNA
  • change cell behaviour by changing cell production rate of certain proteins
• HOW RECEPTORS WORK

  • exist mainly in an inactive state and when bound to an agonist --> binding energy induces a conformational change that switches the receptor to an active state
  • have conformational, desensitized state (safety mechanism that prevents over-exictation)
  • receptor is thousand times bigger than neurotransmitter
  • binds to binding domain --> neurotransmitter or ant other small molecules
  • agonist binding site --> natural ligand ie neurotransmitter or hormone
  • lignad has to be the right size, shape and charge 

  
• DIVERSITY OF NEUROTRANSMITTERS AND THEIR RECEPTORS

  • monoamines

  1. derived from aromatic amino acid --> tyrosine tryptophan or histidine
  2. compounds are all aromatic
  3. dopamine, serotonin, adrenaline, noradrenaline, histamine

  • amines

  1. acetylcholine
  2. not aromatic

  • neuropeptides

  1. small peptides derived from larger precursor proteins chopped up by protease
  2. substance p, endorphins, enkephalins, vasopressin's, oxytocins

  • amino acids

  1. 1-glutamate, gaba, glycine

  • others

  1. nitrous oxide, adenosine, atp
• CRITERIA FOR IDENTIFICATION OF NEUROTRANSMITTERS AND RECEPTORS

  • must be synthesissed by the neuron
  • must be present in synaptic terminal at sufficient concentrations
  • released on pre-synaptic stimulation
  • exogenous application to postsynaptic cell evokes a response
  • mecahsnim exists for its removal from synaptic cleft
• CHOLINERGIC TERMINAL

  
• NICOTINIC CHOLINERGENIC TERMINAL

  • pentameric
  • ionotropic
  • 16 subunits in humans
  • 2 ach sites (muscle receptors)
  • built in cation channel
  • excitatory 
  • fast response (microseconds-miliseconds)
• MUSCARINIC CHOLINERGENIC TERMINAL

  • metabotropic (gpcr)
  • monomeric
  • mm1-5 subtypes
  • binding sites for g proteins
  • 1 ach binding site
  • influences potassium permeability
  • excitatory or inhibitory
  • slow response (milliseconds to seconds)
• GLUTAMATE-GLUTAMATE CYCLE

  • glutamate is a very powerful excitatory neuroreceptor
  • major excitatory receptor in the brain
  • 2 broad classes

  1. inotropic (ligand-gated ion channels/ fast/ iGluR)
  2. metabotropic `9family c gpcr/ slower/ mGluR)
• NMDA RECEPTORS

  • highly permeabile to calcium 
  • blocked by magnesius at rmp  at physiological concentrations 

  1. magensius block of the nmdar can be relieved at repolarized state

  • needs glycine as a coagonist
• NORMAL TRANSMISSION

  • current flow is induced by ampa activation --> loyal depolarisation

  1. can transmit to soma but might not

  • local depolarisation of nada (deactivates it) --> increased depolarisation + influx of calcium (transmit to soma)
  • mGluR1 activation --> long and slow depolarization

  1. lift magnesium block --> leads to more depolarization

  • synpase may become strengthed with repeated use (ltp – long term potentiation)

  
• GABAERGIC TRANSMISSION- gabaA/C

  • ligand gated chloride channels
  • fast
  • pentamers
  • many different subunits
  • when gaba bind to gabaA --> ligand channels open  chlorides crossing the membrane

  1. increases chloride permeability --> inhibition 
  2. ecl often is close to resting membrane potential --> stabilizes the membrane protein close to ecl
  3. leads to hyperpolarixation --> inhibitions
• GABA B

  • family c gpcr
  • slower 
  • 2 subunits --> operate as dimers
  • inhibit voltage gated calcium channels  inhibit transmitter release
  • open potassium channesl  reduce post-synaptic excitability
  • inhibit adenylyl cyclase
• DALES PRINCIPLE

  • neuron only releases one type of neurotransmitter  is not true
  • neurons always releases the same combination at every synapse --> truer but not fully true

  
• AUTORECEPTORS

  • regulation of neurotransmitter release
  • receptors for the neurotransmitter released by nerve terminal
  • when activated --> regulate release of that neurotransmitter
  • some form of inhibition --> negative feedback

  
• HETERORECEPTORS

  • respons to a different neurotransmitter