Ligand gated ion channels and GPCR's

What is a receptor?

What is a receptor?

• Causes a response via cellular change

• Main target for a drug

What is another name for ligand gated ion channels?

Intropic receptors

How long does a ligand gated ion channel take to activate?

Milliseconds

What are the key features of a ligand gated ion channel?

• Form a channel between intracellular and extracellular environment of a cell.

• Number of subunits vary between channels

• Either activate signally or change excitability of the cell

What is an example of a ligand gated ion channel?

Nicotinic acetylcholine receptor

How do nicotinic Ach receptors work?

Agonist binds to the receptor causing Na+ ions to move into the cell and become excited, causing depolarisation.

how does the GABAa receptor control Cl- flow?

• Activation of GABA via an agonist

• Receptor activation increases Cl- movement through ion channel

• Cell membrane hyperpolarizes

• Result is decreased excitability

How does the neuromuscular junction work?

Motor nerves from the spinal cord synapse with skeletal muscle fibres, then each branch forms an end plate region on a motor end plate, initiating contraction.

What are some clinical uses of antagonists?

Tracheal intubation, surgical procedures e.g. abdominal surgery, therapeutic hypothermia.

How can antagonists treat therapeutic hypothermia?

Cardiac arrest, reduce body temp to 32-34 degrees, improves neurological recovery, prevents shivering. Can only be done after anaesthetic as effects whole body.

What is another name for a G-protein coupled receptor?

7 transmembrane receptor or metabotropic receptor

How long does a G-protein coupled receptor take to work?

Seconds

What is a G-protein coupled receptor made up of?

• 7-transmembrane domains

• Extracellular N-terminus

• Intracellular C-terminus

What are key features of G-protein coupled receptors?

• Largest family of receptors in the body

• Highly druggable, almost half of prescription drugs work on them.

What is the basic mechanism of a G-protein coupled receptor?

1. Agonist binds to 7-TM receptor, initiating signalling

2. Signal stimulates G protein, causing it to move along the membrane

3. Effector is activated or inhibited triggers response

What are the different Ga subtypes?

GaS (stimulate), Gai (inhibit), GaQ, Ga12

What are effectors?

Ion channels ad enzymes

What are 2nd messengers?

Ions, intracellular

What are some roles of GPCR?

Vascular tone, airway constriction and relaxation, heart contractility, acid secretion, mood, pathogen defense.

How does vascular tone relate to GPCR?

• Arteries/arterioles contain smooth muscle

• Constriction reduces diameter whereas relaxation increases diameter of the vessel.

• This impacts blood pressure.

• Tone is controlled by: circulating factors (e.g. adrenaline), symp and parasymp nervous system, paracrine factors.