Receptor signaling

Neurotransmitter Receptors

• Two types
  1. Channel -linked receptors: AKA ligand-gated receptors(Direct)
  - NTM (ligand) binds to receptor, receptor changes shape allowing ions to flow across membrane ntm falls off and receptor closes
  - ex: ACh and amino acids
  2. G protein-linked receptors (indirect)
  - indirect because the receptor in this instance is not a ligand gated channel
  - instead, the receptor once its actiavted by the ligand will actiavte a series of steps that can later cause the opening of channels in the membrane (do not directly open channels)
  - ex: biogenic amines, neuropeptides, and dissolved gases

Ligand-gated ion channels (ionotropic) receptors

• ntm binds to receptor, receptor changes shape and opens up allows ions to flow through, ligand falls off, then the receptor closes again

• open for a very limited amount of time

• ntm has to keep binding and opening up channels to cause meaningful graded potential

• can create EPSP’s because sodium moves into the cell depolarizing it and IPSP’s where potassium leaves the cell or chloride enters the cell making the cell more negative and leading to hyperpolarization

• Can have excitatory signals:
  - primarily an influx of sodium
  - sodium moves across the membrane from the interstitial fluid into the cytosol, causing a rise in membrane potential
  - sometimes the excitatory signals also have both sodium ad potassium crossing the membrane at the same time but more sodium crosses than potassium so its still excitatory

• Can be inhibitory signals (decrease likely hood that action potential will fire)
  - ex: potassium, which is normally inside the cell, can not cross and leave the cell, a postive ion leaving a negative charges call will cause the cell to become more negative and hyper polarized
  - ex: chloride has a negative charge and it can move across the membrane into the cel down its concentration gradient which increases the number of negative charges inside the cell which leads to hyperpolarization, which is associated with inhibitory signals

Second messenger Systems (G-protein linked receptors)

• all second messenger systems are indirect

• gets its name because associated with GTP (simialr to ATP but has guansime not adensine)
  - has three phosphates, third phospahte has high energy bond like ATP
  - small G protein can break down GTP to GDP

• Step 1: Neurotransmitter (1 messenger) binds and activates receptors
  - when ntm binds to receptor the receptor changes shape

• Step 2:receptor activates G protein
  - small G protein also changes shape due to ntm binding to receptor
  - GDP molecule falls off and picks up GTP molecule and the GTP molecule causes the small G protein the change shape again and small G protein moves until it comes in contact with adenylate cyclase

• Step 3: G protein activates adenylate cyclase
  - adenylate cyclase is an integral protein that is also an enzyme and is activated by the small G protein with GTP bound to it

• Step 4: Adenylate cyclase converts ATP to cAMP (second messenger)
  - when adenylate cyclase is activated it take ATP and turns it into ANP and attach one end of the molecule to the other
  - this is a cyclic molecule which we call cyclic AMP

• Step 5a: cAMP changes membrane permeability by opening and closing ion channels
  - these channels are not voltage or ligand gated channels, but they are gated channels and regulated by cAMP

• Step 5b: cAMP activates enzymes

• cAMP activates specific genes

• second messenger system: ntm never eneters the cell and ntm can not directly open ligand channel or make anything happen
  - instead it activates receptor that makes things happen in a sequence

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