Cholinergic transmission Flashcards
Where is the distribution of cholingergic transmission?
In pedunclopontine (PPT), laterdorsal tegmntum (LD)
and magnocellular forebrain (BbM ans septohippocmapus).
Wide projections
Found in the periphery at 3 locations: motor synapses in para sym, motor syn in the NMJ and in the brain.
nucleus basal projects to the cortex and hippocampus and striated interneurons have wide projections.
What are the two types of receptors?
Nicotinic and muscarinic
Key features of nicotinic recptors?
pentameric
16 subunits- 9a (1-7,9,10) 4b, y, delta, epsilon
built in ion channels
2 ach sites
us-ms
agonists- nicotine and suxamethonium
antagonist- atracurium, tubocuraine, a BTX
excitatory
are in the cys-loop receptor superfamily
Key features of muscarinic receptors?
monomeric
m1-5 subtypes
5 r types
binding site for a g protein and Ach site
ms-s so larger response
agonist- muscarine, pilocarpine
antagonist- atrophine and hyoscine
What are the main roles of ACh?
pontine nuclei- arousal for sleep/wake
magnocellular forebrain- arousal
Septohippocampal-learning in the short term
striatal interneurons- motor control
What happens to ACh at the cholinergic terminal?
ACh is broken down by the enzyme acetylcholinesterase into choline and acetate. AcyteylcoA hydroylses into coA allowing choline to become ACh. ACh then is packaged into vesicles for synaptic release when and AP is fired. Vesicles then diffuse ACh across the synapse to the post synaptic membrane.
How does synaptic transmission at the nicotinic receptor occur?
The neurons is signalled by dopamine, and have a modulatory action. stimulation Ca ion channel to open. The n is perm to ca so ca influx causes increase in mem dop and causes depol so ap is fired . this enables ACh vesicles to release and diffuse.
How does synaptic transmission at the muscarnic receptor occur?
The muscarinic receptor is a type of G protein-coupled receptor that is activated by ACh. It is widely distributed in the body and involved in numerous physiological processes, including regulation of heart rate, smooth muscle contraction, and cognitive function.
Upon binding of ACh to the muscarinic receptor, a conformational change occurs that activates G-proteins. These G-proteins then interact with downstream effector proteins such as ion channels and enzymes to produce a variety of cellular responses.
M2/4 -signals to AC-Camp- PKA
M1/3/5- signal to PLC and PKC and ca signalling.
Where are skeletal muscle nAChR found?
theres 2.
1- between alpha and delta
2- between alpha and epsilon
they are perm to na, ca, k
binding sites are on the internal side of the subunit.
have to be on an alpha subunit
Where are the agonist binding site on the M2 receptor? How do they work?
M2 domain forms lining of the channel
Outer subunit are agonist binging site and others are reg sites
5 m2 domain. Leu resideu - forms the gate
Rattion of m2 domain during gating
When opens a smaller serine reside moves in favouring ion flow influx rather than leu blocking it.
ser small hydrophilic
leu- large and hydrophobic
in m r agonist binding sites are at the top f the transmembrane domain.
