L6: synaptic transmission Flashcards
why won’t an electric current transmit across a synapse?
it will dissipate in the extracellular space
what kind of junction permits transmission of an electric current between cells?
gap junction
what proteins make a gap junction and what structure do they form?
6 connexins around a central pore make a hemichannel (2 hemichannels come together to form a gap junction)
how is an electrical synapse formed?
through gap junctions
why aren’t electrical synapses the predominant form of communication in the nervous system?
electrical communication not always viable - e.g. current from a small fiber is insufficient to bring larger post-synaptic effector cells to threshold potential
what kind of synapses constitute the predominant form of communication in the nervous system?
chemical synapses
3 key functional differences between electrical and chemical synapses
chemical synapses:
- one-directional (NT on one side, recepter on other)
- synaptic delay (signal converted and back)
- modulated (allowed by multiple steps)
typically how long is the synaptic delay in a chemical synapse?
0.5 - 1 ms
motor end-plate
the post-synaptic receptor region of a muscle cell
interstitial [Ca++]
~2 mM
intracellular [Ca++]
10^-4 mM
voltage-gated Ca++ channels are confined to the terminal region of the pre-synaptic axon called the…
active zone
why is Ca++ ideally suited to play the role of internal messenger in synaptic NT release?
Ca++ has a very large out vs in concentration gradient (2 vs 10^-4 mM)
EPP =
end plate potential
post-synaptic local potential in neuromuscular junction
MEPP =
miniature end-plate potential
cause by spontaneous release of an NT vesicle into neuromuscular junctoin
how many molecules in a quantum of neurotransmitter?
2,000 to 10,000
how can a comparable MEPP be experimentially induced?
by reducing the EPP with a solution of low Ca++ and high Mg++, which is a competitive inhibitor to Ca++ binding
why is neurotransmission “quantal”
neurotransmitter is released from vesicles in packets
T/F an MEPP reflects one quantum of neurotransmitter
true
roughly how many quanta are released in the neurotransmission of a signal
a few hundred
what class of proteins regulate the process of NT exocytosis?
SNARE proteins
synapsin’s role in in neurotransmission
tether NT vesicles at the ready to cytoskeletal structures
synaptobrevin’s role in neurotransmission
in NT vesicle membrane, docks vesicle to syntaxin on the plasma membrane release site
syntaxin’s role in in neurotransmission
in presynaptic plasma membrane, tethers with synaptobrevin on the NT vesicle membrane to dock vesicle at release site
synaptotagmin’s role in in neurotransmission
senses Ca++ elevation and triggers NT vesicle fusion
why is NT vesicle release a “kiss & run” process
synaptic vesicles fuse, release contents, and retract back into synapse to be refilled and reused
SNAP25’s role in in neurotransmission
executes fusion of NT vesicle
plasma membrane bound, similar to syntaxin
what are the roles of the following SNARE proteins in neurotransmission:
- synapsin
- synaptobrevin
- syntaxin
- SNAP25
- synaptotagmin
- synapsin: tether vesicles to cytoskeleton
- synaptobrevin: on VM, docks to PM
- syntaxin: on PM, docks vesicle
- SNAP25: on PM, executes fusion
- synaptotagmin: binds Ca++, triggers fusion
3 main pathways for neurotransmitter removal from synaptic cleft
- diffusion
- degradation
- re-uptake
ACh-E
acetylcholinesterase
-hydrolyzes ACh into acetate and choline
what is the enzyme that breaks down ACh in the synaptic cleft?
ACh-E
acetylcholinesterase
what are the products of ACh-E hydrolysis of ACh?
acetate
choline
does ACh-E reside free in the synaptic cleft or on the post-synaptic membrane?
it varies, depicted either way
what is the rate of ACh hydrolysis by ACh-E in the synaptic cleft?
~40,000 ACh/s
how is NT re-uptake accomplished?
through Na+ coupled transporters
secondary active transport
what are two types of NT receptors on post-synaptic membranes?
ionotropic receptors
metabotropic receptors
are nicotinic receptors ionotropic or metabotropic?
ionotropic
nicotinic receptors bind which NT?
ACh
how does an ionotropic NT receptor work?
NT binding causes conformational shift and opening or closing of a path for ions to flow
what kind of NT receptor is appropriate for fast-acting effects, e.g. “run for your life!”
ionotropic
what kind of NT receptor is appropriate for sustained effects, e.g. slowing heart rate for sleeping
metabotropic
what is the advantage/disadvantage of ionotropic receptors?
fast acting / no amplification or modulation
how do metabotropic NT receptors work?
NT binding induces activation of second messenger proteins and an enzyme reaction chain that results in opening of ion channels
what is the typical first link in a metabotropic NT receptor chain
G-protein
are serotonin receptors ionotropic or metabotropic?
metabotropic
how do G-proteins usually work
G-protein activation causes release of GDP and binding of GTP, which causes α subunit to dissociate from βγ complex, and subunits are now available to interact with effector proteins, typically producing second messengers. the G-protein resets after GTP has been hydrolized and α regroups with βγ
what is the advantage / disadvantage of metabotropic NT receptors?
amplification & modulation / sluggish
what kind of potential is activated by NT binding to post-synaptic receptors?
local potential
T/F NT receptors are mostly located at the junctional region
true
what is the effect of adding the poison d-turbocurarine to the synapse?
blocks ACh receptors
T/F the machinery that converts an electrical response to a chemical signal and back is all confined to the synaptic region
true
what is a reversal potential
an experimentally clamped ∆V at which a NT-receptor binding and opening of ion channels causes no net change in current flow across membrane – this ∆V reversal depends on what ions the opened channels are permeable to, and how permeable it is to these ions
I net = I1 + I2 +… = 0
g1 (V1 - E1) + g2 (V2 - E2) + … = 0
what is the Na+ / K+ permeability of ACh opened channels?
1.25
if reversal potential = -15 mV and the NT opened channels are permeable to Na and K, what is the ratio of Na+ / K+ permeability in the channels?
I net = I Na + I K = 0 (at reversal potential) g Na (V - E Na) + g K (V - E K) = 0 g Na (-65) + g K (80) = 0 g Na / g K = 80/65 = 1.23
EPSP =
excitatory post-synaptic potential
NT opened channels with ∆V reversal < ∆V resting will produce what kind of post-synaptic potential?
IPSP
inhibitory post-synaptic potential
(hyperpolarizing)
NT opened channels with ∆V reversal > ∆V resting will produce what kind of post-synaptic potential?
EPSP
excitatory post-synaptic potential
(depolarizing)
EPSP =
excitatory post-synaptic potential
depolarizing
IPSP =
inhibitory post-synaptic potential
hyperpolarizing
T/F reversal potential = threshold potential
false - reversal potential is the equilibrium potential of NT opened channels, which indicates whether an NT effect will produce an EPSP (∆V rev > ∆V rest) or an IPSP (∆V rev < ∆V rest)
what are two inhibitory synapse mechanisms?
hyperpolarize
stabilize
how can an inhibitory synapse function without producing and IPSP?
synaptic inhibition can be achieved by opening channels permeable to an ion with an equilibrium potential near V resting (e.g. Cl-); this will make conductance to Cl- dominant and will clamp the ∆V resting near E Cl-, resisting change in ∆V from that value
equilibrium potential of Cl- =
~-65 mV
-61log(112/10)
T/F a given NT always elicits the same post-synaptic response (excitatory or inhibitory)
false - dependent on the receptors and ion channels involved, a given NT can produce EPSPs or IPSPs in different circumstances
name the 6 major classes of amino acids
ACh biogenic amines amino acids neuroactive peptides gases purines
4 biogenic amines that function as neurotransmitters:
norepinephrine
dopamine
serotonin
histamine
4 amino acids that function as neurotransmitters:
glutamate
aspartate
GABA
glycine
2 gases that function as neurotransmitters:
NO
CO
2 purines that function as neurotransmitters:
ATP
Adenosine
T/F in the neuromuscular junction the post-synaptic response to a Single nerve impulse is sufficiently large to activate voltage-gated Na+ and K+ channels and initiate an action potential
true
(while true at the neuromuscular junction, this is not the case in a typical nerve cell, which sums many EPSPs and IPSPs)
why is the neuron a center of integration, and not just a simple relay link along a chain?
the dendritic tree and soma of the cell do not contain the density of voltage gated Na+ and K+ channels to initiate and action potential – this machinery exists at the axon hillock and down the axon, where the local potentials of the dendrites and soma are summed and an action potential is initiated (or not)
where in the neuron is the density of V-gated Na+ channels sufficient to initiate and action potential?
-axon hillock and axons
not dendritic tree and soma
how does τ change over the course of a post-synaptic local potential (EPSP or IPSP) ?
τ is shorter when channels open (Rm decreases)
τ is longer when channels close (Rm increases)
so the ∆V has a quick spike and a slow return to rest
temporal summation
burst of PSPs over a short period can summate and reach a larger ∆V even though individual PSPs may be quite small
spatial summation
two or more PSPs from different locations converging on the same neuron can add up in magnitude to reach a larger ∆V even though individual PSPs may be much smaller
2 factors that can help a PSP reach the axon hillock with greater amplitude
- proximity to hillock
- diameter of fiber (lower τ higher λ)
what is the ICF / ECF ratio of:
Cl-
Ca++
Cl-: 10 / 112
Ca++: 10^-4 / 2
T/F inhibitory synapses often occur on the cell body because this is where they are most effective in preventing an action potential from occurring
true
T/F spatial summation may occur between an inhibitory and excitatory local potential
true
T/F temporal summation occurs between EPSPs generated by one synapse
true
T/F spatial and temporal summation of excitatory local potentials is less likely if the membrane has more leakage channels
true
T/F temporal summation is more likely if the membrane capacitance is low
false - if membrane capacitance is low, τ = RmCm will be low, conduction velocity will be high, and an EPSP will be more likely to run away along the membrane too quickly for the next EPSP to catch it and summate.
when axon radius decreases, how does this affect the ∆V τ and λ ?
no change τ = RC ~1/A x A
decrease λ ~ sq.rt (r) (Rm~1/A; Ri~1/Vol)
when axon radius increases, how does this affect ∆V τ and λ ?
no change τ = RC ~1/A x A
increase λ ~ sq.rt (r)
(because Rm~1/A; Ri~1/Vol)
T/F EPSPs can temporally summate at a single synapse to yield a membrane potential more positive in value than any one EPSP
true
T/F ACh muscarinic receptors are the target of circulating antibodies in myasthenia gravis
false
nicotinic receptors at neuromuscular junctions
(probably N1)
T/F acetylcholine is the major transmitter released from post-ganglionic sympathetic fibers
false - ACh and NE are both major transmitters released from post-ganglionic sympathetic fibers
(ACh is major NT released from somatic motor fibers)
T/F the channel opened by acetylcholine in the muscle endplate is selective to Na+ and K+
true (though a little more selective for Na+)
