Neurotransmitte rs A. Criteria 1. must mimic presynaptic effects if administered exogenously 2. must be released during activity of presynaptic neuron 3. action must be blocked by same agents that block natural transmission
Jan 04, 2016
NeurotransmittersA. Criteria
1. must mimic presynaptic effects if administered exogenously2. must be released during activity of presynaptic neuron3. action must be blocked by same agents that block natural transmission
NeurotransmittersB. Activity
1. fast-acting (direct) - ionotropic- receptor coupled directly to ion channel
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NeurotransmittersB. Activity
2. slow (indirect) - metabotropic- receptor coupled to membrane receptor- activation of second messenger pathways
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NeurotransmittersB. Activity
2. slow (indirect) - metabotropic- or modulates opening of channels in response to voltage changes (neuromodulation)
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NeurotransmittersC. Classification
1. small moleculesa. acetylcholine (ACh)b. biogenic aminesc. amino acids
NeurotransmittersC. Classification
2. neuropeptides (from all areas of nervous system)a. also from hypothalamus, pituitary, and other organsb. are often neurosecretory hormonesc. also endorphins and enkephalins
- bind to same receptors as opiates- endogenous opioids
NeurotransmittersC. Classification
3. most are highly conserved4. fast-direct transmitters
- only one type synthesized by individual neuronsa. ACh
- cholinergic neurons (i. e., neuromuscular junction)- curare is antagonist
NeurotransmittersC. Classification
- acetylcholinesterase breaks ACh down to acetate and choline- choline recycled in presynaptic neuron- blocked by some toxins (Sarin, tetanus)
NeurotransmittersC. Classification
4. fast-direct transmittersb. glutamate
- excitatory in vertebrate CNS
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NMDA receptors are ionotropic glutamate receptorsthese modulate Ca++ channels
NeurotransmittersC. Classification
4. fast-direct transmittersc. GABA-A (-aminobutyric acid)
- inhibitory at ”glutamate” synapses
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d. glycine
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- inhibitory- can modulate glutamate
d. glycine- inhibitory- some have chloride ionophore function
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Biogenic Amines/Monoamines
A. Serotonin - derived from tryptophan
Selective Serotonin Reuptake Inhibitors
- slow, indirect transmission - metabotropic
Biogenic Amines/Monoamines
B. Catecholamines - derived from tyrosine
- adrenergic neurons1. epinephrine/adrenaline (hormone and neurotransmitter)
Biogenic Amines/Monoamines
B. Catecholamines - derived from tyrosine2. norepinephrine/noradrenaline (hormone and neurotransmitter)
- many psychoactive drugs mimic NE- amphetamines- cocaine (prevents inactivation of NE)
3. dopamine
Biogenic Amines/Monoamines
C. Release and uptake1. similar release to ACh2. rapid inhibition following release
a. reuptake to presynaptic neuronsb. monoamine oxidase in presynaptic neuron
RegulationDesensitization/Down-regulation
- initially a decrease in affinity- long-term becomes loss of receptors
RegulationSuper-sensitivity/Up-regulation
- seen in synapses that are rarely used
RegulationLong-term potentiation
- an increase in the strength of synaptic transmission with repetitive use that lasts for more than a few minutes- in hippocampus can be triggered in less than 1 second of intense synaptic activity
RegulationLong-term potentiation Model:
1. afferent stimulus causes release of glutamate2. glutamate binds to NMDA and non-NMDA receptors on postsynaptic membrane (Na+ influx)3. EPSP causes removal of Mg++ which normally hinders Na+ and Ca++ influx4. Ca++ influx leads to activation of postsynaptic protein kinase, which induces an LTP.
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