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82 Cards in this Set
- Front
- Back
synapse
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- specialized site of contact of a neuron with another neuron or an effector
- locus = where one cell influences function of another - synaptic cleft = space separating neurons |
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2 synaptic functions
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- synaptic transmission
- synaptic plasticity |
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synaptic transmission
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- site where presynaptic signal has an effect on a postsynaptic cell
- usually chemical but can be electrical - excite or inhibit postsynaptic cells |
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chemical synapse
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- cells not connected
- relay on diffusion of NT - unidirectional - discontinuity between cells - synaptic cleft barrier to direct electrical communication - presynaptic releases NT that rapidly diffuse to postsynaptic where they bind to receptor molecules that generate electrical or chemical change - excitatory or inhibitory = depend of type of NT and receptor - high level plasticity = important for development and learning - amplify current flow = depends on amount of NT released and number of receptors on postsynaptic |
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electrical synapse
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- electric currents from one cell flow directly into next cell, changing membrane potential
- connected by gap junction - fast synaptic transmission - not polarized = bidirectional - synchronizing ability |
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synaptic plasticity
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- ability to change functional properties of synapses
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gap junction
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- low resistance pathways to allow current to flow
- specialized locus where protein channels bridge the gap between 2 cells, directly connecting cytoplasm - electrical synapse - electrical coupling - differ in strength = larger it is, stronger the coupling - connexons of 2 adjacent membranes |
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connexons
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- regular array of channel structures
- composed of hexamors of the protein cannexin - hemichannels = connexons join together to form channels - low resistance pathways - can close in response to electrical or chemical changes |
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electrocytes
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- modified muscle cells that lost capacity to contract
- produce about 10V to 15V - stacked in electric organ - nicotinic acetylcholine receptors - compared to voltaic pile |
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synaptic vesicles
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- stores neurotransmitters
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active zones
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- dark tufts of electron dense material on cytoplasmic side of presynaptic where synaptic vesicles release their NT
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postsynaptic densities
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- reflect accumulation of NT receptors and scaffolding proteins
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scaffolding proteins
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- help organize receptors and other proteins at synpase
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NT receptors
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- transmembrane receptors
- work in one of two ways = ionotropic, metabotropic |
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ionotropic
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- chemical synapse
- movement of ions to generate action potential - binding of ion transmitter opens ion channel - much quicker - produce fast changes in membrane potential by directly increasing permeability to ions |
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metabotropic
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- trigger signaling cascade of second messengers in post synaptic cell
- relatively slow - long lasting modulatory effects |
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synaptic potential
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- transitory, graded change in resting membrane potential
- control neuronal excitability - neural integration - neurons output determined by sum of all neuronal inputs - depolarizes = excitatory postsynaptic potential (EPSP) - hyperpolarizes = inhibitory postsynaptic potential (IPSP) |
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excitatory postsynaptic potential
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- rising phase and exponential decay
- temporal summation = resultant EPSP of peripheral nerve A stimulated repeatedly and rapidly - spatial summation = combination of simultaneously occurring EPSP produced by different nerves - smaller postsynaptic membrane at synapse smaller - presynaptic membrane release less NT - in CNS most common NT is glutamate |
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inhibitory postsynaptic potential
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- drive membrane potential away from threshold
- produce temporal or spatial summation |
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neuronal integration
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- neuron's output
- spatial and temporal summation of EPSP and IPSP - spatial = many fibers converge on single postsynaptic - summation = waves of transmitter release |
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functional chemical synapse
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- action potential arrives at terminal buton
- opening of voltage gated Ca channels - binding to ionotropic receptors - binding to metabolic G protein coupled receptors |
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fast chemical synapses
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- workhorse of synaptic mechanism
- neuromuscular junction = model system for chemical synaptic transmission - functions as relay synapse - anatomical simplicity - large synaptic response - summary of events in chemical synaptic transmission |
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fast IPSP
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- hyperpolarizing
- increase in permeability to Cl ions - mediated by GABA and glycine - NT usually |
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chemical synaptic transmission
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- action potential depolarized presynaptic terminal and opens voltage gated Ca channels
- Ca enter - triggers release ACh to synaptic cleft - NT bind to specific receptor proteins - ligand-gated channels open, allowing ion flow = produce EPSP that spreads decremental - depolarize muscle fiber membrane to threshold and initiate a muscle fiber action potential - action of NT terminated by enzymatic degradation or by reuptake - choline transporter retrieves choline into presynaptic terminal for ACh resynthesis |
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acetylcholinesterase
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- enzyme synthesized by postsynaptic muscle fibers and located in synaptic cleft
- destroys ACh |
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during EPSP
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- Na and K increase simultaneously
- synaptic current = produces depolarization that is the rising phase of an EPSP - drive membrane toward a potential near zero |
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aceytlcholine
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- synthesized from choline and acetyl choline A
- ACh taken up into vesicles - docked or anchored |
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NT release
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- stimulus = depolarization
- amount released increase with depolarization - dependent on influx of Ca ions |
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Ca has 3 effects
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- binds to calmodulin
- binds synaptobrevin/synaptophysin complex - another protein in syaptotagmin binds to Ca at high concentrations |
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Ca binds to calmodulin
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- complex activates calmodulin-dependent protein kinase which is a tyrosine kinase
- hydrolyzes ATP - synapsin 1 + P disrupt interaction with actin - vesicles released |
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binds synaptobrevin/synaptophysin complex
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- synaptobrevin is V snare that binds to congate T snare
- V and T snares are docking proteins |
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another protein in syaptotamin binds Ca at high concentrations
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- synaptotagmin 1 = integral membrane glycoprotein
- functions as calcium sensor to synchronize NT release - calcium dependent exocytosis activator protein |
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clastoidal bacteria
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- associated with botulism and tetanus
- secrete protease that serve as neurotoxins to break down snares |
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vesicular docking and fusion
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- release NT
- targeting = vesicles move to active zone - docking = V and T SNAREs bind, vesicle irreversibly docked - Ca entry = Ca binds to synaptotagmin - fusion = synaptogmin triggers membrane fusion and exocytosis |
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vesicle recycling
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- allows synaptic vesicles to reform and prevents plasma membrane from expanding
- synaptic vesicles are mobilized or targeted to move to release sites - dock and are primed until Ca trigger fusion - endocytosis = a pinching off from terminal membrance |
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membrane retrieval/vesicle recycling
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- NT released into the cleft
- clathrin helps selectively retrieve vesicular membranes along with dynamin - adaptin interacts with clathrin - dynamin promotes reuptake of vesicles - some require ATP |
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2 modes of fusion
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- classical
- kiss and run |
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classical
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- vesicular membrane merges with terminal membrane and new vesicle is later retrieved by endocytosis
- selectively retrieves vesicular membranes - two proteins aid: clathrin and dynamin |
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kiss and run
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- docked vesicles opens a fusion pore to release transmitter into synpatic cleft without becoming completely integrated
- faster and may predominate at lower rates of release |
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proteins in vesicle release
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- synapsin attaches vesicle to actin cytoskeleton and released when phosphorylated
- SNAREs - Munc18 and complexion prime docked vesicles - synaptotagmin = Ca bind to trigger formation of a fusion pore that may lead to exocytotic fusion - rab 3 is active in vascular mobilization and recycling and may inhibit excessive fusion and release - cytoplasmic proteins may disassemble SNARE |
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SNARE proteins
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- mediate fusion of cellular transport vesicles
- vesicles (v SNARE) - target (t SNARE) |
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3 SNARES
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- syntaxin 1, SNAP-25 in cell membrane and synaptobrevin in vesicular membrane
- syntaxin and synaptobrevin anchored by C-terminal domains - SNAP-25 tethered via cysteine-linked palmitoyl chains - 4-alpha-helix bundle = 1 for syntaxin 1, 1 for synaptobrevin, 2 for SNAP-25 |
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t SNARE
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- target
- located in membranes of target compartments - hold docked vesicle at active zone - syntaxin and SNAP |
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v SNARE
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- vesicular
- incorporated into membrane of transport vesicle - intertwine with terminal membrane - syaptobrevin |
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postsynaptic potentials
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- spread decrementally because they don't result from action of voltage gated channels
- ACh receptor = ligand gated Na-K channel - no current flow = NT open channels |
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metabotrophic synapse action
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- doesn't directly open ion channels
- 7 transmembrane segments in receptors - G protein coupled receptor - binding of NT to GCPR cause conformation change - alpha subunit release GDP and binds GTP = becomes activated - alpha subunit binds to adenyl cyclase = change ATP to cAMP - cAMP activates protein kinase which releases catalytic - GTP can also bind to some kind of channel or intracellular effector |
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synaptic delay
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- neurons can transmit action potential at 150m/s
- neuronal transmission across synapses is slower time to open Ca channels, release NT, diffusion across cleft, binding receptor, change postsynaptic - rate limiting step |
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2 major kinds of NT
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- small-molecule NT = amines and amino acids
- neuropeptides |
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amino acid
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- most synapses use
- most fast EPSP = glutamata - most fast IPSP = GABA or glycine |
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biogenic amine
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- found in relatively few neurons
- slow actions that modulate neural activity - contain amine with a calcite group benzene ring with 2 adjacent hydroxyl groups - synthesis starts with amino acid phenylalatine |
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peptide
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- chains of amino acids
- synthesized in cell body of neuron - propeptide = large precursor polypeptide - large dense-cored vesicles = contain propeptide molecules - exocytosis of large dense-cored vesicles not at active zone - digested by nonspecific extracellular peptidases - locally retrieved or rapidly resynthesized = resupply - present the least - co-released - may regulate transmission of pain information - presynaptic inhibition of enkephalin (peptide) decreases the amount of NT release from the second neuron - enkephalin decreases synaptic transmission |
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multiple receptors
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- different postsynaptic actions at different postsynaptic cells
- ACh excites skeletal muscle via EPSP but inhibits cardiac muscle via hyperpolarizing IPSP - ACh receptor of skeletal muscle = nicotine - ACh receptor of heart muscle = muscarinic |
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termination of NT action
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- enzymatic destruction
- reuptake |
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enzymatic destruction
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- acetylcholinesterase (AChE) = terminates the postsynaptic effects of ACh and provides choline
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reuptake
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- norepinephrine
- Na entry down electrochemical gradient to drive transmitter uptake against concentration gradient - actively transports molecules across membrane against concentration gradient |
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acetylcholine
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- neuromuscular junction
- excitatory at neuromuscular junction - nicotonic = iontropic - muscarinic = metabotropic - biogenic amine - also in PNS and preganglia of autonomic system neurons and post ganglionic of parasympathetic |
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choline acetyltransferase (ChAT)
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- synthesized within perikaryon
- transferred into terminal buton via axoplasmic flow or anterograde movement via kinesin - makes ACh with choline and acetyl CoA - choline rate limiting factor = supplied by blood with uptake transporters in presynaptic membrane |
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ACh synthesis
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- in axon terminal
- acetyl CoA synthesized in mitochondria in terminal buton - catalyzed by choline acetyltransferase |
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ACh breakdown
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- taken into vesicles by specific vesicular transporters
- on vesicle membrane - vesicular ACh transporter - antiport with H+ - storage of ACh = quanta - packaged with ATP - ACh remains bound for brief period then released - degraded by ACh esterase located on postsynaptic membrane and cleft - choline recaptured by presynaptic membrane and reused |
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botulism toxin and barbiturates
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- inhibit ACh release
- barbiturates act as CNS depressants - decrease ACh levels in certain areas of Alzheimer patient's brain |
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nicotonic receptors
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- found on motor end plates of skeletal muscle
- all sympathetic and parasympathetic ganglionic neurons - hormone producing cells of adrenal medulla - always excitatory - nicotine causes rapid depolarization - curate and some snake venoms block nicotonic R - effects prolonged by nerve gas and organophosphate - destroyed in myasthenia gravis - ionotropic - glucoproteins - 5 transmembrane domains surrounded by ligand gated channel - alpha domains bind ACh - 4 membrane spanning regions: M1, M2, M3, M4 - M2 is polar and lines the channel - conformational change in shape that opens the ion channel to allow Na and K flow - inward Na larger than K outward - creates EPSP - prolonged exposure = inactivated or desensitized |
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muscarionic receptors
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- parasympathetic targe cells, blood vessels in skeletal muscles, some sweat glands, heart
- mushroom alkaloid - metabotrophic receptor - R is inhibited by atropine - simlatory and inhibitory - ACh binding to cardiac muscle slows the heart - ACh binding to smooth muscle in GI tract increases motility - linked to G protein - M2 domain activates G protein inhibitory protein that causes opening of K channels and depolarization lasting seconds, and decreases in contraction rate |
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norepinephrine
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- biogenic amine
- metabotrophic - excitatory or inhibitory depending of R type - PNS = main transmitter of preganglionic cells of sympathetic nervous system - CNS = brain stem, limbic system, some ares cerebral cortex - good feeling NT - release enhanced by amphetamines - removal from synapse blocked by tricyclic antidepressants and cocaine |
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norephinephrine synthesis
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- mostly in nerve terminal
- sotred in synaptic vesicles with ATP - adrenergic nerve endings - transported into synaptic vesicles by vesicular monoamine transporter - VMAT integral membrane protein in vesicular membrane - equal affinity for norephinephrine and epinephrine - enzymatically inactivated by monoamine oxidase (MAO) |
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monoamine oxidase (MAO)
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- removes amine group
- bound to outer membrane of mitochondria or synaptic cleft - iron containing enzyme that exist as 2 isozymes A and B that have different affinities for various amines as substrates |
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monoamine oxidase inhibitors (MAOI)
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- powerful antidepressant drugs
- used only when others fail |
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- catechol-O-methyl transferase (COMT)
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- enzymatically inactivate norepinephrine
- methylation of 3-hydroxyl group of catechol ring - postsynaptic membrane, synaptic cleft, pre-synaptic cell |
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norepinephrine reuptake transporter
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- removes norepinephrine from synaptic cleft
- presynaptic membrane - ATP used to drive transport - amphetamines increase uptake |
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2 major classes of NPR adrenergic receptors
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- both in 7 transmembrane domain receptor super family
- beta - alpa |
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beta
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- inhibitory
- G protein coupled receptor - heart and coronary blood vessels, adipose tissue, vascular and airway smooth muscle |
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alpha
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- activated by receptor occupancy
- stimulatory - G protein coupled receptor - blood vessels serving skin, pupils, and visceral organs, membrane of adrenegic axon terminals |
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dopamine
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- biogenic amine
- excitatory or inhibitory depending on receptor - midbrain and hypothalamus - metabotrophic - feel good NT - reuptake blocked by cocaine - deficient in Parkinson's disease - maybe involved in schizophrenia |
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seratonin
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- biogenic amine
- mainly inhibitory - metabotrophic - brain stem, midbrain, hypothalamus, limbic system, cerebellum, pineal gland, spinal cord - play role in sleep, appetite, nausea, migraines, mood regulation - prozac blocks reuptake and relieves anxiety and depression |
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glumate
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- amino acid
- major excitatory NT of CNS - ionotropic - important in learning, memory, and motor control - reuptake transporter in presynaptic membrane - types: AMPA EPSP, NMDA Ca second messanger |
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induction and maintenance of LTP
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- NMDA receptors blocked at resting potential by Mg ions
- receptors activated by drug N-methyl D asparate - non NMDA receptors open to produce fast EPSP - depolarization releases Mg - Ca enters NMDA receptor channels and act as second messenger in cell activating Ca dependent protein kinase - increase presynaptic NT release |
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GABA
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- gamma amino butyric acid
- main inhibitory NT of brain - GABA a = ionotrophic * opens chloride channels IPSP - GABA b = metabotrophic * IPSP - hypothalamus, purkinje cells, retina, and olfactory bulb - inhibitory effect enhanced by alcohol and valium |
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glycine
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- major inhibitory NT of spinal cord
- ionotrophic - strychnine blocks receptor resulting in convulsions and respiratory arrest |
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peptides
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- endorphines
- p substances |
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endorphins
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- generally inhibitory
- metabotrophic - wide spread in brain - natural opiate - inhibits pain by inhibiting substance p |
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p substance
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- excitatory = mediates pain transduction in PNS
- metabotrophic - dorsal root ganglia = pain affecters |
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gases as NT
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- nitric oxide (NO) = ubiquitous signaling molecule
- involve in vasodilation, neurotransmission, immune response - excitatory - metabotrophic - spinal cord, adrenal gland, nerves to penis - release potentiates stroke damage |
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NO produced by 3 iso-enxymes of NO synthase
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- endothelial nitric oxide synthase (eNOS) regulates vascular tone and smooth muscle tension
- neuronal nitric oxide synthase (nNOS) functions as a diffusible neurotransmitter - cytokine inducible NO synthase (iNOS) acts as an effective defense mechanism during inflammation, but it also involved in arthritis and multiple sclerosis |