Lecture 2: Drug Targets - Receptors Flashcards
Is signal transduction faster in Skeletal muscle or Heart muscle?
Signal transduction is faster in Skeletal muscle (milliseconds). Signal transduction in Heart muscle is slow (several seconds).
Does acetylcholine hyperpolarise or depolarise skeletal muscle?
Depolarises skeletal muscle. Hyperpolarises cardiac muscle.
Does cardiac muscle have nicotinic acetylcholine receptors or muscarinic acetylcholine receptors?
Muscarinic acetylcholine receptors. Nicotinic acetylcholine receptors are present in skeletal muscle.
Put the four receptor types in order, from fastest to slowest process.
- Ligand-gated ion channels (milliseconds)
- G-protein coupled receptors (seconds)
- Kinase-linked receptors (hours)
- Nuclear receptors (hours or more)
Do Ligands bind to the intracellular or extracellular part of a membrane receptor?
Extracellular part.
How many acetylcholine molecules are needed to activate a nicotinic ACh receptor?
2 as there are 2 binding sites which both must be bound to ACh to activate the ligand-gated ion channel.
How many subunits does a Nicotinic ACh receptor have?
Five. They are a mixture of four different types: alpha, beta, gamma and delta. And there are two alpha subunits which are always adjacent to the ACh binding sites.
Each subunit of a Nicotinic ACh receptor contains how many membrane-spanning alpha-helices?
Four. Inserted into the membrane.
The alpha helices of the subunits that span the membrane of a Nicotinic ACh Receptor are called what? And which contains a leucine?
M1, M2, M3 and M4.
Each subunit has a leucine in their M2 helix. These line the centre of a pore to form a “gate”.
Will the ACh binding site be found in the N-terminal domain or the C-terminal domain of a Nicotinic ACh receptor subunit?
The N-terminal domain.
Glu and Thr residues in pore of a Nicotinic ACh receptor provide electron pairs. Do they attract or exclude anions (Eg. Cl-) ?
They exclude anions.
They attract cations.
In a resting state, what do leucines of the M2 alpha helices of the subunits do?
Leucines block the pore which means that the gate is closed.
What happens to the alpha subunits when ACh binds to Nicotinic ACh receptors?
A conformational change occurs to the extracellular part of the nAChR which twists the alpha subunits and causes the M2 segments to swivel out of the way, thus opening the channel.
Do anaesthetics bind competitively or allosterically to Nicotinic ACh receptors?
Allosterically. They do not bind at the N-terminus of the subunit like ACh does, but in between the M2 and M3 segments.
Where do anaesthetics that affect nAChR bind?
It binds to the loop between M2 and M3 alpha helices of a subunit.
