1-Synaptic Transmission Flashcards
info flow within a neuron
- dendrites- collect signals
- cell body- integrates incoming signals + gen outgoing
- axon- passes signal to dendrites
info flow between neurons
- electrical (minority) or chemical (neuron-neuron, neuron-muscle) synapse
- presynaptic neuron
- synaptic cleft
- postsynaptic
structure of electical synapse
1+ gap junction channels b/t pre and postsynaptic membranes permeable to ions and small moles
6 connexin > connexon > gap junction
bidirectional, fastest, low selectivity
significance of electrical synapses
@ most tissues - nervous system, myocardial, intestinal smooth muscle, cochlea
mediate chemical coupling in a network
synchronize electric activty with pop of neurons
intercellular chemical signaling
- hormones- neurohormone if substance released into the bloodstream by neuron
- neurotransmitters- local distribution by diffusion, released at synapse by neuron, synaptic mechanism when post synaptic cell very close, paracrine mechanism when several near by cells
morphology of synapses
- presynaptic terminal with active zone where vesicular release happens
- synaptic cleft
- postsynaptic site
neuron-neuron pathway
- transmitter syn and stored in vesicles
- action potential invades presynaptic terminal
- depolarization = opening of voltage gate Ca channels
- influx of Ca thru channels
- vesicles fuse with presynaptic membrane
- transmitter released via exocytosis, vesicle recycles via endocytosis
- transmitter binds receptor in postsynaptic membrane
- open or closing post syn channels, ligand gated ion
- postsyn current excitatory or inhibitory potential
- removal of transmitter via glial uptake or enzymes
- retrieval of vesicular membrane from plasma membrane
SNARE complex
synaptic release machinery
transmembrane proteins in vesicles and presyn plasma membrane for helix complex to dock and fuse vesicle
recovery of presynaptic terminal
- repolarize as K leaves thru voltage gated K channels
- voltage gated Ca channels close so Ca stop flowing into synaptic terminal
- free Ca removed from cytoplasm via sequestration
- vesicle recycled
Ca sequestration
three ways
1. diffusion
2. Ca binding proteins
3. transported to internal Ca stores
4. pumped or transported outside cell via secondary active antiporter
vesicle endocytosis
recyling
- clathrin recruited to vesicular membrane
- clathrin triskelia assemble into coat that curves membrane
- dynamin ring forms to pinch off membrane
- coated vesicle translocated by actin fila
- Hsc-70 and auxilin uncoat vesicle
fusion is rapid but recylcing takes more time so if prolonged firing activity then exhause the vesicle pool
types of neurotransmitters
small molecule
- amino acids - glutamate (excitatory), GABA (inhibit), glycine, serine, aspartate
- acetylcholine
- amines- histamine, monoamines (serotonin), catecholamines (dopamine, norepinephrine, epinephrine
syn and packed into small clear core vesicles at nerve terminals
low frequency stimulation
classes of postsynaptic receptors
- ionotropic- ligand gated ion channel, rapid changes in mem potential, local
- metabotropic- G protein coupled, slow change in mem potential since multi steps, diffusive, signal amp
EPSP
excitatory postsynaptic potential
fast response mediated by ionotropic receptors and glutamatergic synapse
brings potential Vm closer to threshold, depolarization
glutamate gated channels permeable to Na and K but Na>K
will decay over time
IPSP
inhibitory postsynaptic potential
fast response mediated by ionotropic receptors
GABA receptors/gated ion channels permeable to Cl chemical driving force > Vrest so influx of Cl to hyperpolarize IPSP
away from threshold, also decay
slow postsynaptic response
mediated by metabotropic receptors so can either decrease (excite) or inc (inhibit) conduction thru Cl/K channels
G protein or second messangers, may link to ionic channels
synaptic delay
pause b/t arrival of action potential in presyn and onset of potential change in postsyn
-events leading to fusion in presyn
-diffusion of transmitter across cleft
-activation of postsyn channels
1-2 msec at fast chem synapses (ionotropic) and longer with metabotropic
dopamine clearance
many abused drugs like cocaine bind bind to dopamine transporters @ presyn terminals = inc of synaptic DA level
summation of synaptic responses
@ CNS - indiv EPSP too small for action potential threshold in postsyn cell
graded effect of all synapses is summed in time and space at initial axon segment until sufficiently depolarized and voltage gated sodium channels open
unconventional transmitter
- purines- adenosine when ATP degraded, needs purinergic receptor
- NO- not packed into vesicle since gas
- endocannabinoids- product of enzymatic degradation of membrane lipids
neurotransmitter criteria
- packed into synaptic vesicles
- Ca dependent release
- bind to specific receptors
neuropeptide synthesis
precursors made in nucleus then packed into large dense core vesicles for transport to terminal
released with high frequency stimulation along with small molecule
neuromuscular junction
motor axon terminals embedded in grooves in muscle fiber surface
has junctional folds for postsyn membrane and multiple active zones
NMJ transmission
- action potential
- Ca enters voltage gate channels
- Ach released
- Na enters postsyn folds to create local current b/t depolarized end plate and adjacent muscle plasma membrane
- muscle fiber action potential initated then propogated in membrane
- Ach degradation
nicotinic acetylcholine receptors
nAchR aka Ach gated ion channels are ionotropic, permeable to Na and K but Na>K
unique features neuromuscular transmission
-each indiv muscle fiber innervated by one motor neuron
-only excitatory not inhibition input
-only one type neurotransmitter Ach
-only one type receptor nAch R
-multi active zones at one terminal
-multi terminals on one muscle fiber
-strong transmission to ensure AP
toxins targetting NMJ
- botulism- in soil, water, foodborne, targets motor neurons to paralyze = muscle weak, botox
- tetanus- wound contamination, targets interneurons to disinhibit/hyperexcite = tetanic contractions
both cleave SNARE proteins
eaton lamber syndrome
presynaptic disorder
-freq in pts with small cell carcinoma of lung
-antibodies to voltage gated Ca channels in presynaptic terminal of somatic motor nerves
-less Ca enters presyn terminal so less Ach released = muscle weakness
myasthenia gravis
postsynaptic disorder
-severe muscle weakness from antibodies vs nAchR in NMJ so dec # of functional postsyn receptors
use neostigmine to indirectly enhance function of existing AchR by inc extracellular Ach levels, reversible Ach inhibitor
acetylcholine receptor blockers
- tubocurarine
- curare- poison from bark of south american tree
- alpha-bungarotoxin from peptide of venom of banded krait snake, irreversibly blocks nAchR
cholinesterase inhibitors
- edrophonium, short acting inhibitor to dx myasthenia gravis, long acting inhibitors to treat
- organophosphorus compounds aka sarin gas and pesticides irreversibly bind
