PSYC 3030

• cAMP mechanism of action

  1. first messengers: neurotransmitters, drugs, etc

  2. ^ bind to receptors; coupling factors to adenylyl cyclase

  3. cAMP second messenger --> ion channels and cAMP-dependent protein kinase (PKA)

  4. ^ distributes to substrate proteins for the protein kinases

  5. biological responses
• how is cytoplasmic Ca2+ concentration regulated at rest?

  regulated by Ca2+ - Mg2+ ATPases (calcium pumps)

  
  

  Ca2+ second messenger interacts w intracellular Ca2+ binding protein CALMODULIN to regulate a number of proteins

  
  

  ex. Ca2+/ calmodulin-dependent protein kinase II (CaM-K II)

  ex. protein dephosphorylation (reverse of kinase effects)
• what are some examples of second messengers

  cAMP

  cGMP

  Ca2+

  IP3
• what are the three physiological result options after the third messenger?

  1. rapid mediatory processes

  2. short-term modulatory processes

  3. long-term modulatory processes (new proteins)
• what do protein kinases do?

  protein kinases phosphorylate substrate proteins (third messengers)
• biochemical/second messenger cascade system

  ligand -> receptor --activates-> G protein -> effector enzyme --signals--> second messengers --> protein kinases --> substrate proteins --> cellular effects
• what is a second messenger

  intracellular molecule regulated by extracellular signalling

  
  

  the first messenger is the ligand

  cellular effectors are the third messengers

  g protein isn't considered a messenger
• best characterized G proteins

  cAMP, cGMP, DAG/IP3; they have toxin sensitivity

  
  

  two toxins typically used for study and identification of G proteins: cholera (causes diarrhea), pertussis (whooping cough)
• what is the mechanism of action of metabotropic receptors?

  - agonist binds to receptor

  - activates g protein by reaching out to touch it, stimulating GDP-> GTP

  - the heterotrimer becomes a dimer because the α subunit (the big one) dissociates (the α unit and the dimer can go and effect the target protein)

  - the α subunit acts as an enzyme and eventually hydrolyzes (removes a phosphate group from) GTP, restarting the cycle
• why are g proteins named g proteins?

  because of the GTP or GDP that aids in their regulation
• structure of G-proteins

  generally have 3 subunits: α (20 subtypes divided into 4 subfamilies) β (5 subtypes) γ (8 subtypes)
• which has more variety of outcome, ionotropic or metabotropic receptors?

  metabotropic
• process of metabotropic receptors

  - when the ligand binds, the receptor reaches out to stimulate g proteins

  - g proteins can activate other effector proteins

  - these effector proteins can either be effector enzymes (affects the production of second messengers) or the g protein can just directly influence the ion channel
• do metabotropic receptors have protein subunits?

  NO; theyre made of a single protein w 7 transmembrane domains (winds 7x back and forth through the membrane); no pore

  
• GABAa receptor

  - Cl-

  - inhibitory
• NMDA receptor

  - Ca2+ is second messenger

  - 4 subunits
• nicotinic ACh receptor

  - ionotropic

  - has Na+ ion channel, produces excitatory effect and is why you feel the effects of smoking in ur head

  - 5 subunits (is the cover photo)
• do ionotropic receptors have subunits?

  YES they have 4-5 heterogenous subunits, creating variety in function

  they have one or more binding sites (ORTHOSTERIC SITES), the rest are ALLOSTERIC, which modulate the function of the receptor

  
  

  the star photo thats the cover of the course is the birds eye view of this
• tyrosine kinase receptors are independent units T/F

  FALSE; they activate when they come together (they look like little arms+hands); when they come together they phosphorylate each other
• what is a protein kinase?

  an enzyme that phosphorylates (adds phosphate group(s)) proteins
• what are the 3 tyrosine kinase receptors?

  1st: trkA; nerve growth factor (NGF); one of the most commonly studied

  2nd: trkB; brain-derived neurotrophic factor (BDNF); common in CNS and neurotrophin-3 and -4 (NT-3 and -4)

  3rd: trkC; neurotrophin-3 (NT-3)
• what are tyrosine kinase receptors activated by?

  neurotrophic factors
• what are the 3 receptor superfamilies?

  1. tyrosine kinase receptors -- not directly involved in neurotransmission (Rather respond to neurotrophic factors)

  2. ionotropic receptors/ligand gated receptors -- involved in fast neural signalling ∴ very short latencies

  3. metabotropic/G-protein coupled receptors -- slow but sustaining signalling ∴ longer latencies
• 3 steps of neurotransmitter inactivation

  1. enzymatic breakdown

  2. reuptake (by presynaptic cell)

  3. uptake (by glial cells)

  
  

  many psychoactive drugs block the reuptake mechanisms
• heteroreceptor vs autoreceptor

  hetero: respond to neurotransmitters etc from neighbouring cells

  auto: respond to neurotransmitters etc from only their own cell; provide negative feedback, can help prevent overstimulation
• how do action potentials increase in intensity?

  they are all or none for firing, so more stimulation= higher frequency of firing rather than stronger

  rapid firing -> more neurotransmitter released
• docking SNARE proteins

  
• after Ca2+ channels open after the action potential (endocytosis in the synapse), what happens to prevent the surface from just growing and growing

  exocytosis creates endosomes in the cell from the membrane
• What ion channel is opened during neurotransmitter exocytosis after the action potential?

  Ca2+ channels (voltage gated)
• different types of neurotransmitters

  amino acids

  monoamines (single amine group)

  acetylcholine (quaternary amine)

  neuropeptides (3-40 amino acids)
• there are many subtypes of receptors


  ex. dopamine has 5 subtypes of receptors
• is there a lot or a little mitochondria in the axon terminal

  A LOT
• organization of the brain

  
• how is affinity expressed


  the michaelis-menten constant (Km): extracellular concentration of substrate that yields 1/2 of the max velocity (Vmax) of the membrane transport of the substrate for a given amount of the transporter protein

  low Km= high affinity
• transport across membranes

  - passive diffusion: determined by concentration gradient, no energy required

  - facilitated diffusion: movement against the concentration gradient, initiated by binding of substrate; types: ion channels, voltage or ligand gated ion channels, uniporter (one), antiporter (2, opposite directions), symporter (2, same direction), ATP-coupled active transporter (ex. ATPase, Na K pump-- 3 Na+ OUT, 2 K+ IN)
• what are the 3 parts of a phospholipid

  1. polar head (-); phosphate

  2. glycerol backbone

  3. 2 non-polar fatty acid tails

  
  

  they are amphipathic ∴ semipermeable
• what is axoplasmic transport

  - movement of various organelles to and from the cell body of a neuron through the cytoplasm in the axon

  - anterograde transport: away from cell body

  - retrograde transport: towards cell body

  - fast: 200-400 mm/day, highly dependent on ATP and oxygen

  slow: 1-10 mm/day, ~80% of all materials carried in axon

  - its the diagram of the little guys walking on a little road back and forth in the axon
• golgi apparatus


  consists of stacks of flattened membranous sacs that play an active role in the modification, storage, sorting and secretion of the proteins produced by the cell
• what is splicing and when does it occur?

  splicing is a post-transcriptional process that removes internal sequences that will not be translated into proteins in the cell

  results in mRNA, which exits the nucleus into the cytoplasm and binds to a ribosome to initiate translation
• what are the 3 requirements for the activation of gene expression

  1. transcriptional activator proteins

  2. transcription factors ( proteins not encoded to the same DNA to which they bind; bind to promoter regions to determine the boundaries of transcribed DNA)

  3. the enzyme RNA polymerase (activates transcription process)