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56 Cards in this Set
- Front
- Back
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What are the 3 requirements of a NT?
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1. Present in presynaptic neuron
2. Released from presynaptic terminal in Ca-dependent manner 3. Binds to specific receptors on postsynaptic cell |
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What is 1 difference between hormones and NTs?
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Hormones act distally, NTs act locally
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What are 2 categories of NTs? What kind of responses do they mediate?
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1. Small-molecule NTs - rapid, local
2. Neuropeptides - slower, longer distances |
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What are 5 examples of small-molecule NTs?
(3 are biogenic amines) |
1. Ach
2. Amino acids BIOGENIC AMINES 3. Catecholamines 4. Serotonin 5. Histamine |
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What is the structure of the nicotinic AChR at the NMJ?
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5 subunits (2 alpha, 1 beta, 1 gamma, 1 delta)
1 Ach binding site on each alpha subunit (2 total) |
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How are neuronal nicotinic AChRs different structurally than those at the NMJ?
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Neuronal have 3 alpha and 2 beta subunits
NMJ have 2 alpha, 1 b, 1 g, and 1 d subunit |
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What is the major excitatory NT is CNS?
What receptors mediate fast responses to this? |
Glutamate
Ionotropic glutamate receptors: NMDA receptors and AMPA/kainate receptors |
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What is the major inhibitory NT in the CNS?
What two receptors mediate GABA responses? |
GABA
ionotropic GABAa receptors (fast?) and metabotropic GABAb receptors (slow?) |
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How are AMPA/Kainate, NMDA, and GABAa receptors similar to nicotinic AChR?
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All are ligand gated ionotropic channels that are pentameric complexes
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What is the response of Glutamate binding to AMPA/kainate receptors?
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opening of cation-selective ion channel that is equally permeable to Na and K (Erev=0) --> depolarization
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What is the result of binding glutamate to NMDA receptors?
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Slow EPSC
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What is the result of AMPAR and NMDAR simultaneous activation?
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summation of the individual responses (quick spike followed by slow wave)
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What is the role of AMPARs?
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Fast excitatory responses in postsynaptic cell
Glutamate binds, opens cation selective channel (Na and K) --> depolarization |
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How are NMDARs structured to provide slow EPSCs (and serve as 'coincidence detectors'?)
What do receptors need to be activated? (2 things) |
Voltage-dependent Mg block of outer mouth of pore
1. Glutamate binding 2. Movement of Mg by depolarization of postsynaptic cell, result of multiple firing events of presynaptic cell |
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What molecules are NMDA receptors permeable to?
What are the effects of this? |
Equally permeable to Na and K
Also permeable to Ca --> Ca influx --> can trigger downstream signaling events |
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What is the structure of metabotropic receptors and how do they signal?
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7 transmembrane-domain receptors formed by single polypeptide chains
Signal via G-protein coupled cascade |
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What happens when GABA binds a GABAa receptor?
Structure of a GABAa receptor? |
Opening of Cl channel (Erev -75) --> hyperpolarization
pentameric, ionotropic |
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What happens when GABA binds GABAb receptors?
Structure of GABAb receptor? |
G protein pathway --> opening of K channels (Erev = -90) --> delayed hyperpolarization
7 transmembrane domain receptor, metabotropic |
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How do opioids evoke IPSPs?
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Facilitate K channel opening by acting on metabotropic receptors
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What type of vesicles are Ach and amino acid NTs packaged into?
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Small clear vesicles, 40-60 nm diameter
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What type of vesicles are biogenic amine NTs packaged into?
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Small dense-core vesicles (40-60 nm diameter) or larger dense-core vesicles (60-120 nm)
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What type of vesicles are neuropeptide NTs packaged into?
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large dense-core vesicles, 90-250 nm diameter
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What is the process of synthesis, packaging, and recycling of small molecule NTs? (6 steps)
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1. Synthesis of enzymes in cell body
2. Slow axon transport (0.5-5 mm/day) 3. Transport of precursors into nerve terminal 4. Synthesis and packaging of NT in nerve terminal 5. Release and diffusion of NT 6. NTs cleared by specific uptake transporters, recycled |
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What is the process of synthesis, packaging, and recycling of neuropeptide NTs? (4 steps)
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1. Synthesis of propeptides in cell body, put into vesicles
2. Fast axon transport into terminal (400 mm/day) 3. Enzymes modify to produce peptide NT 4. NT diffuses out, degraded by proteolytic enzymes (Except Ach) |
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What are co-transmitters?
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multiple NTs that are present in the same synaptic terminal
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When are small molecule NTs fired vs. neuropeptides
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Small molecule NTs at low frequency stimulation, more localized Ca concentration
Neuropeptides at high frequency stimulation, more diffuse Ca concentration |
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How is Ach synthesized?
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acetyl CoA + choline using enzyme choline acetyltransferase (ChAT)
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How is Ach action terminated?
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Hydrolyzed by acetylcholine esterase (AchE) in synaptic cleft
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What is the effect of blocking Ach esterase?
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desensitization of Ach receptors --> neuromuscular paralysis --> death
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What is the role of Glutamate in CNS?
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Major excitatory NT in CNS
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How is Glutamate generated?
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Generated from glutamine by glutaminase, packaged into synaptic vesicles
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What is the glutamate-glutamine cycle?
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Glutamate in synaptic cleft removed by glial glutamate transporters (EAAT) --> converted to glutamine by glutamine synthetase --> shuttled back to synaptic terminal --> back to glutamate by glutaminase
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What happens if there is excessive release of glutamate?
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Glutamate excitotoxicity
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What is the role of GABA in CNS?
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Inhibitory
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How is GABA made?
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From glutamate by glutamic acid decarboxylase (GAD)
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How is release GABA cleared?
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uptake transporters
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What mediates intracellular GABA degradation?
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GABA aminotransferase
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Why is inhibitory neurotransmission important?
What do GABAergic drugs do? |
Prevents run away excitation
Act as sedatives, prevent epileptic seizures |
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What is the role of Glycine and where does it act?
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Inhibitory
Acts in brain stem and spinal cord |
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How is glycine produced?
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From serine by serine transhydroxymethylase
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How is glycine removed from the synaptic cleft?
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Specific transporters
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How is Dopamine produced? (2 steps)
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1. Tyrosine --> DOPA via tyrosine hydroxylase
2. DOPA --> Dopamine by DOPA decarboxylase |
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Where are dopamine receptors and what do they do?
What happens with degeneration of dopaminergic neurons? |
Receptors in substantia nigra in basal ganglia, initiation and termination of movements
Parkinson's |
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How is NE generated?
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Dopamine --> NE via dopamine b-hydroxylase
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Where are NE neurons and what do they do?
What does amphetamine do? |
Located in locus coeruleus, role in modulation of arousal states
Promotes release of NE |
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How is Epinepherine generated?
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NE --> E by phenylethanolamine-N-methyltransferase
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Where are epinepherine-containing neurons?
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rostral medulla
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How is Histamine generated?
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Histidine --> histamine by histidine decarboxylase
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Where are histamine-containing neurons located?
Function? |
Tuuberomammillary nucleus in hypothalamus
Maintains awake state |
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How is Serotonin generated? (2 steps)
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1. Tryptophan --> 5-hydroxytryptophan by tryptophan-5-hyroxylase (RATE LIMITING)
2. --> serotonin |
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Where are serotonergic neurons located and what do they do?
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Raphe nuclei
Modulate sleep, wakefulness, and mood |
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How do antidepressants work?
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Block serotonin reuptake transporter
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What is the conductivity of the NMDA receptor regulated by? (2 things)
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Mg (blocks channel)
Glycine |
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How is the GABAb receptor different than the other metabotropic receptors?
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GABAb = heterodimer
Most metabotropic receptors are single polypeptide chains |
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What is the difference between the synthesis/packaging of small molecule NTs vs. neuropeptides?
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Small molecule NTs synthesized and packaged in nerve terminal
Neuropeptides synthesized in cell body as pro-peptides, the transported and activated in nerve terminal |
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What is the difference in the method by which small molecule NTs and neuropeptides are cleared from the synapse?
Exceptions? |
Small-molecule NTs = cleared by reuptake transporters, recycled
Neuropeptides = proteolytically degraded, not recycled Ach is the exception |
