Synaptic Transmission Flashcards
what are the two kinds of synapses?
electrical and chemical
electrical synapses occurs as a result of
INTERcellular flow of current between cells attached via connexins
chemical synapses occur via
chemical release from a pre synaptic membrane and attached to post synaptic membrane
GAP junctions
Specialized structures that provide a direct, private pathway connecting the cytoplasm of adjacent cells and allow electrical current to pass directly between neighboring cells.
what is the structure of a GAP junction
6 protein subunits (connexins) surrounding a central channel creates a connexon which combines with another cells connexon to form the GAP junction pathway
what is the direction of transmission for chemical and electrical synapses?
electrical is bi-directional
chemical is uni-directional
which type of transmission is faster?
- electrical is faster and has no delay
- chemical has a synaptic delay of about 0.5 msec
electrical synapses have a high degree of
certainty
i.e. impulse in the presynaptic cell will flow directly into the post synaptic cell without being blocked
GAP junctions allow cardiac and smooth muscle cells to
contract synchronously
how do GAP junctions differ from membrane channels?
- normal state is OPEN
- channel spans two cell membranes
- both ends of the channel are intracellular
- both cations and anions can pass
the closing of GAP junctions is mediated by
- high intracellular Ca2+ (death signal)
- high intracellular H+ (low pH)
- depolarization of one of the cells (significant change in electrical charge)
what are the four processes of chemical synaptic transmission
- release of chemical transmitter from pre-synaptic terminal
- diffusion of transmitter to post-synaptic membrane
- binding of transmitter to post-synaptic receptor
- inactivation or removal of transmitter
a molecule is considered a neurotransmitter if
- if its synthesis occurs in the neuron itself
- found in a presynaptic membrane
- released into synaptic cleft and causes a change in the post-synaptic membrane
- effect is the same whether released exogenously (drugs) or endogenously
- once released its removed for reuse or degraded
what are the three classes of neurotransmitters
- neurotransmitters
- neuroactive peptides
- neuromodulators
what are examples of neurotransmitters
- acetylcholine (ACh)
- amine transmitters: norepinephrine, epinephrine, dopamine, serotonin, histamine)
- gases: nitric oxide
what are examples of neuroactive peptides
-opioid peptides (enkephalins, endorphins, dynorphins)
- nonopioid peptides (substance P, vasoactive intestinal polypeptide (VIP), cholecystokinin(CCK))
what are examples of neuromodulators?
- purine nucleotides (ATP)
- purines (adenosine)
neuromuscular junction (chemical synapse)
synaptic connection between a motor neuron and muscle fiber
* also called myoneural junctions or motor endplates
in humans the neuromuscular synapse is always
excitatory, never inhibitory
what is the active zone of a neuromuscular junction
synaptic vessels containing neurotransmitters accumulate around presynaptic dense bars
post synaptic folds
located opposite the dense bars
what causes the thickening of the post synaptic membrane
high density of post synaptic receptors of ACh
what does an action potential induce at the synaptic knob
voltage gated Ca2+ channels to open causing the release of acetylcholine
what receptors bind acetylcholine and what does it induce
- nicotinic ACh receptor site proteins
- ligand gated Na+/K+ ion channels to open
the amount of transmitter released is very sensitive to
the amount of calcium entering the cell
what effect does magnesium have on transmitter release?
Mg2+ competes with Ca2+ causing a reduction in transmitter release
acetylcholine is synthesized from
acetyl coenzyme A and choline made from serine using choline acetyltransferase
* occurs in cytoplasm
where does most of the choline used for formation of acetylcholine come from
reuptake after acetylcholine binds to its receptor on the post synaptic membrane
hemicholinium
compounds that block the reuptake of choline
transmitters are loaded into vesicles by
an active transport mechanism
- ATP is used to transport H+ into the vesicle
- the H+ proton gradient then uses VACh transporter to exchange H+ for ACh
what are the three proteins found on the cell membrane involved with neurotransmitter release
- Syntaxin – A SNARE Protein located on the presynaptic membrane that directly interacts with synaptobrevin (on the vesicle) and SNAP-25 to form the SNARE complex, which helps vesicle fusion.
- SNAP-25 – A SNARE Protein that anchors to the presynaptic membrane stabilizing the interaction between syntaxin and synaptobrevin an helps bring the synaptic vesicle close to the membrane for fusion
- Voltage-Gated Ca²⁺ Channels – increases the Ca²⁺ concentration which activates synaptotagmin, triggering vesicle fusion and neurotransmitter release.
what are the two proteins found on the synaptic vessel involved with neurotransmitter release and what is their role
- Synaptotagmin – binds to the Ca²⁺ ions that enter through voltage-gated calcium channels and triggers rapid vesicle fusion with the presynaptic membrane, leading to neurotransmitter release
- Synaptobrevin (VAMP) - A SNARE Protein essential for vesicle docking and fusion that interacts with proteins on the presynaptic membrane to form the SNARE complex
synaptic delay
around 0.5 msec for presynaptic depolarization to produce a postsynaptic conductance increase primarily due to vesicle fusion and neurotransmitter release
quantum of ACh
the amount of ACh contained in one vesicle (about 2000 molecules at rest)
Miniature End Plate Potentials (MEPPs)
spontaneous release of a small amount of ACh that does not excite the muscle fiber to threshold
Nicotinic Acetylcholine Receptors
- ACh receptors located in skeletal muscle end plates that are activated by nicotine and blocked by curare and are directly gated by ACh, meaning ACh binding opens the ion channel allowing sodium (Na⁺) in and potassium (K⁺) out
where does acetylcholine bind on the Nicotinic Acetylcholine Receptors and what does binding cause
ACh binds to both α subunits of the 5 subunit structure (α₂βγδ) which opens the channel to allow Na⁺ and K⁺ to move freely with equal conductance through the channel
Ionotropic Receptors (Direct)
type of receptor that is physically part of a ligand-gated ion channel and opens when a specific chemical (ligand), such as a neurotransmitter, binds to them
Metabotropic Receptors (Indirect)
type of receptor found on the surface of cells where neurotransmitter binding triggers G-proteins and second messengers to illicit cellular changes
Excitatory Postsynaptic Potential (EPSP) is caused by
presynaptic action potential that releases about 300 vesicles of ACh at once
what does an EPSP lead to
endplate potential and if enough depolarization occurs, an action potential
endplate potential
ACh binds to receptors on the muscle cell, causing a large change in the muscle’s membrane potential (Em).
At the peak of the EPP (-30 mV)
- there’s no net current flow into or out of the muscle as a whole
- there is equal Na+ entering and K+ leaving
Inhibitory Postsynaptic Potentials
Inhibitory ion channels are permeable to Cl- and K+ where Cl-
moves into the cell and K+ moves out of the cell making the cell more negative, hence causing a local hyperpolarization
spatial summation
when multiple synapses in nearby locations are stimulated simultaneously
Temporal summation
when the same channel is repeatedly opened (the presynaptic cell receives many impulses in a row), thereby altering the membrane potential further before it has the time to return to normal
what are the three ways neurotransmitters are deactivated
- degradation: enzymes located in the synaptic cleft break down the neurotransmitter into a substance which has no effect on the receptor channel
- reuptake: the neurotransmitter can reenter the presynaptic cell through channels in the membrane.
- autoreceptors: receptors on presynaptic terminal bind neurotransmitters and inhibits further neurotransmitter release or synthesis (decreasing Ca2+ channels)
eserine, edrophonium and neostigmine
drugs that block the action of Acetylcholine esterase (hydrolyzes acetylcholine for reputake of choline)
carbachol
mimics ACh but cannot be hydrolyzed by acetylcholine esterase therefore prolonging the activation of receptors
organophosphate and military nerve gases
inhibits acetylcholine esterase
Myasthenia Gravis
autoimmune disease that is characterized by the decrease in ACh receptors causing smaller EPPs
Curare
an alkaloid from South American plants is a competitive blocker of ACh at the receptor binding site
D-tubocurarine
used to relax skeletal muscles in anesthesia
α–bungarotoxin
from the venom of a Taiwanese snake, binds to the ACh receptor and prevents activation by ACh.
Succinylcholine
ACh derivative used as a depolarizing paralytic drug that binds to the acetylcholine receptor and opens the channel for a long time because succinylcholine is not hydrolyzed well by acetylcholine esterase
α-latrotoxin
(from black widow spider venom) causes massive Ca2+ independent
release of transmitter
Tetanus toxin
cleaves synaptobrevin/VAMP preventing neurotransmitter release
Botulinum toxins
cleaves synaptobrevin/VAMP, syntaxin, or SNAP-25preventing neurotransmitter release
In the CNS an EPSP produced by a single synapse
is not enough to cause an action potential therefore inputs of several synapses must be summed (spatially or temporally) to produce an action potential.
