Cholinergic neurotransmission Flashcards
Functions
Role in movement by direct control of skeletal muscle (at NMJ)
autonomic modulation of timing and tension of cardiac and smooth muscle (postganglionic parasympathetic)
nAChRs
11 identified
all pentamers
muscle-type receptors (at NMJ) made up of alpha1, beta1, epsilon (or gamma in embroyos), and delta
neuronal subtypes are a combination of the alpha2-10 and beta2-4 can be homo- or heteromeric
mAChRs isoforms
M1/3/5 are Gq
M2/4 are Gi
Gq increases IP3 and DAG, increases IC [Ca], decreases K+ currents
Gi decreases [cAMP] and [Ca]
all found in CNS, M1-4 also found in periphery
Ganglia
Parasympathetic ganglion located within effector organs
sympathetic innervation can be adrenergic, cholinergic, dopaminergic.
depending on the receptor innervated by the postganglionic neurone, the muscle contraction can be stimulated or inhibited
NMJ
A motor unit is the motoneurons and all the muscle fibres it innervates. they function as one unit.
Focal innervation = 1 synapse per muscle fibre. each fibre only innervated by 1 motoneuron
8-10x ACh needed released to ensure contraction when motoneurons fires
ACh synthesis
In cytosol
Acetyl-CoA + Choline -> ACh catalysed by choline acetyltransferase
choline and acetyl-CoA are dietary precursors
Metabolism and recycling
produces choline and acetate
80% of choline reuptake by neurone. This is the rate limiting step in synthesis
Pathways
Pontine cholinergic system projects from the pontine in the lateral segmental area to several parts of the midbrain and thalamus and is important for motor function
the medial septal group projects to the crotexes and is important for cognition
Effect of manipulating ACh system on cognition, and age related [ACh]
ACh depletion contributes to normal age-related cognitive decline.
ACh agonists found to improve cognitive function. Same with AChE’s in AD. improved vigilance task performance, with faster responses and less errors.
ACh antagonists impair memory similar to AD
