synaptic transmissions Flashcards
two main types of synapses
electrical - physical low-resistance connection allows charge transfer
chemical - ligand intermediary
- ionotropic - ligand binds to channels and change their conductance
- metabotropic - ligands bind to protein receptors separate from ion channels and change conductance via other intermediaries
excitatory synapses often show
asymmetry in the dense material around the synaptic cleft with denser material on the post-synaptic side (Gray’s type I)
inhibitory synapses often show
less dense by symmetric densities on both dies of the synapse (Gray’s type II)
connexins
transmembrane proteins that serve as the subunits of connexons, the transcellular channels that permit electrical and metabolic coupling btw cells at electrical synapses
allow direct flow of ions
properties of electrical synapses
- fast
- allow ions and molecules (ATP, cAMP) to pass
- largely unaffected by neuromodulators
- non-inverting (presynaptic and postsynaptic cell do the same thing)
- often bidirectional
properties of chemical synapses
- slower
- no direct exchange of ions or molecules
- affected by neuromodulators (reuptake inhibitors, toxins, receptor agonists)
- can invert signal (excitatory presynaptic potential can lead to inhibitory postsynaptic potential)
- unidirectional
two main roles of gap junctions
1 spike synchronization - spikes do not pass easily but sub-threshold voltage fluctuations do. they can influence spike timing and cause synchronous spiking bc the transmission has very low latency
2 coordination of oscillations - coordinated rhythmic activity among interneurons may entrain the firing of principle cells resulting in oscillations. in the hippocampus, interneurons may orchestrate gamma oscillations
coupling coefficient/coupling ratio
measures the strength of electrical coupling btw two cells
is frequency-dependent
steps in chemical synaptic transmission
- neurotransmitter release
- receptor binding
- ion channels open or close
- conductance change causes current flow
- postsynaptic potential changes (EPSP and IPSP)
- summation and threshold
- no action potential or action potential
after release into the synaptic cleft, a neurotransmitter can…
- bind to receptors
- diffuse away
- re-uptake back into presynaptic terminal
- taken up by glia
- enzymatic breakdown
how to determine what ions are involved in the current
1 use voltage clamp to determine the reversal potential
2 test how varying ion concs affects the reversal of the evoked current
end plate current (EPC)
a macroscopic postsynaptic current resulting from the summed opening of many ion channels; produced by neurotransmitter release and binding at the motor end plate
end plate
the complex postsynaptic specializations at the site of nerve contact on skeletal muscle fibers
end plate potential (EPP)
depolarization of the membrane potential of skeletal muscle fiber, caused by the action of the transmitter acetylcholine at the neuromuscular synapse
calcium chelators
bind and inactivate calcium ions
BAPTA - rapid inactivation (reduction of EPSP magnitude)
EGTA - slower inactivation (no change in EPSP)
calcium conc at the release site is reduced via
- diffusion (fast)
- Ca2+ buffers (moderately fast)
- transport into organelles via pump or ion exchange (slow)
- Na-Ca exchange mechanism (slow)
microdomains provide
1 high Ca2+ conc needed to activate vesicle release
2 a mechanism for fast inactivation of release
synaptic delay
time btw action potential in presynaptic cell and start of EPSP
possible sources of delay
1 opening of voltage-gated calcium gates in presynaptic terminal
2 diffusion of calcium into the terminal
3 response of vesicle docking and release mechanism
4 diffusion of neurotransmitter in cleft
5 opening of ligand-gated channels in post-synaptic cell
vesicle lifecycle
1 vesicles formed via budding from endosome or transported from cell body forming reserve pools of loaded vesicles
2 vesicles dock near release site
3 vesicles become primed for fusion
4 calcium influx causes vesicle fusion
5 vesicle becomes part of cell wall
6 pocket of cell wall is drawn into the cell (endocytosis) to become a new vesicle
7 new vesicle remains in cell or joins endosome
kiss and run
vesicles may only partly fuse with the cell membrane during exocytosis
neurotransmitter is released, but the vesicle doesn’t become part of the cell wall and instead gets pinched off and reformed into a vesicle
SNAREs
SNAP receptors
proteins that are found on two membranes and are responsible for fusing the two membranes together, vesicle fusion
SNAPs
soluble NSF-attachment proteins
a protein that attaches the enzyme NSF to SNARE complexes to allow NSF to dissociate the SNARE complexes
synaptotagmin
normally bound to the vesicle, to act as the calcium sensor, actually triggers vesicle fusion when calcium concs rise
clathrin
aids in the process of endocytosis
steps in membrane budding during endocytosis
1 adaptor proteins connect clathrin to vesicular membrane
2 clathrin triskelia assemble into coat, curving membrane to form coated pit
3 assembled clathrin cage constricts lipid stalk connecting two membranes
4 dynamic ring forms and pinches off lipid stalk
5 coated vesicle translocated by actin filaments
6 Hsc70 and auxilin uncoat the vesicle
fast axonal transport mechanisms use
microtubules as highways
bidirectional
vesicles tagged for direction and destination
kinesin
protein that handles anterograde (cell to synapse) transport
dynein
protein that handles retrograde (synapse to cell) transport
