Neurotransmitter Review Flashcards
Steps in neurotransmitter release, action, and inactivation
- Calcium influx due to an action potential triggers
- Neurotransmitter release/ exocytosis
- Postsynaptic receptor (ion channel or GCPR)
- Presynaptic receptor
- Reuptake by a transporter (druggable target)
- Degredation (druggable target)
- Reuptake and metabolism by glia
- Vesicle membrane recycled (endocytosis so the membrane doesn’t get huge and floppy)
- Dense core granule vesicle (ie peptides)
- Release away from active zone
Where is acetylcholine found?
ACh is the neurotransmitter at all vertebrate neuromuscular junctions because all motor neurons are cholinergic. ACh is the neurotransmitter for all preganglionic neurons and parasympathetic postganglionic neurons because the autonomic nervous system is also cholinergic
Uses for acetylcholine
CNS circuits are also implicated in cognitive process such as attention, learning, memory, and arousal
The two main cholinergic pathways
the local circuit cells (those which are morphologically arrayed wholly within the neuronal structure in which they are found) and projection neurons (those that connect two or more regions).
ACh projections
Two important projections are in the basal forebrain cholinergic complex: medial septal nucleus (ms) and nucleus basilis (bas), both of which project to the hippocampus and cortex
What synthesizes ACh
ACh is synthesized by choline acetyltransferase
What degrades ACh
ACh is degraded by acetylcholinesterase
What is responsible for reuptake of ACh
The high affinity choline transporter (ChT) is responsible for reuptake of ACh
Details about the choline transporter
ChT has 13 transmembrane domains, with intracellular N and C terminals
Alzheimer’s disease
Alzheimer’s disease is a condition characterized by changes in cognition, attention, learning, and some types of memory. Muscarinic receptor antagonists disrupt short term memory. ChT and VAChT are lost (or there is at least a decreased ability to detect them). Three of the four FDA drugs approved for treatment of the symptoms of Alzheimer’s disease are cholinesterase inhibitors: galantamine, rivastigmine, and donepezil.
Cholinergic receptors
Cholinergic receptors include muscarinic (GPCR) and nicotinic (ligand gated ion channels)
Muscarinic receptors
Muscarinic receptors are densely concentrated in the brain; all subtypes are expressed (M1,3,5 is coupled with Gq and M2,4 is coupled with Gi).
Nicotinic receptors
Nicotinic receptors consist of five subunits oriented around a central cation channel
Nicotinic receptor types
Muscle type receptor: (α1)2β1ɣδ
Ganglion type receptor: (α3)2(β4)3
Neuronal receptor: (α4)2(β2)3 and (α7)5
Neuronal nicotinic receptor (α4)2(β2)3
This receptor is present pre and postsynaptically and has increased cation permeability to Na+ and K+. This neuronal subtype is responsible for high affinity binding of nicotine and has known pathological significance in addition to tobacco with Alzheimer’s disease. Activation is slow and desensitization is slow
Neuronal nicotinic receptor (α7)5
This receptor is present pre and postsynaptically and has increase cation permeability to Ca2+. It plays a role in schizophrenia and Alzheimer’s disease. Activation is fast and desensitization is fast
Role of catecholamines
arousal, mood, and central regulation of blood pressure
Examples of catecholamines in the brain
norepinephrine, dopamine, and epinephrine
Where does the locus ceruleus target
It targets the cerebral cortex, hippocampus, thalamic nuclei, cerebellum, and spinal cord
What is the purpose of locus ceruleus projections to the spinal cord?
Locus ceruleus projections to the spinal cord are thought to be important in regulation and processing of perceptual information
What are the lateral tegmental noradrenergic neurons
The lateral tegmental noradrenergic neurons are part of the reticular activating system and are important for arousal (why amphetamine causes arousal in humans). They are also important in the action of antidepressant drugs
What is the rate limiting step in the synthesis of norepinephrine?
tyrosine hydroxylase is the rate limiting step
What is responsible for the reuptake of norepinephrine?
norepinephrine transporter (NET)
What degrades norepinephrine in the presynaptic terminal?
MAO or COMT
Where is MAO located?
The outer mitochondrial membrane
What receptors is norepinephrine a substrate for?
α1, α2, β1, and β2 adrenoceptors