Topic 3: synaptic transmission Flashcards
What is a synapse?
A specialised junction where one part of the neuron contacts and communicates with another neuron or cell type.
What does electrical synapses allow for?
Direct transfer of ionic current from one cell to the next.
Where do electrical synapses occur? and what is the time delay of current that flows from cell to cell?
-At specialised sites called gap junctions
-negligible time delay
Where do gap junctions occur? and what is the distance between the membranes of 2 cells in a gap junction?
in nearly every part of the body, separated by about 3nm
What is the narrow gap junction spanned by?
clusters of special protein called connexins –> there are about 20 different subtypes of connexins
What makes up a connexon? and a gap junction
6 connexins make up a connexon, and 2 connexon form a gap junction channel
What does the gap junction channel allow?
allows ions to pass directly from cytoplasm of one cell to cytoplasm of another cell.
What direction does ionic current pass through jap junctions?
can travel in both directions
What happens when 2 neurons are electrically coupled and an AP in presynaptic neuron?
AP in presynaptic neuron causes a small amount of ionic current to flow across the gap junction channels into the other neuron. This current causes an electrically mediated postsynaptic potential (PSP) in second neuron. PSP by single synapse usually small, about 1mV
What does deletion of a critical gap junction called connexin36 (Cx36) do?
Did not alter the neurons’ ability to generate oscillations and APs but did diminish the synchrony of these events because of the loss of functional gap junctions
How wide is the synaptic cleft?
20-50nm, 10 times the width of the gap junctions
What is the synaptic cleft filled with? and what is its function?
matrix of fibrous extracellular protein, one function of this matrix is to serve as a “glue” that binds the pre- and postsynaptic membranes together.
how big are the synaptic vesicles? and what do they store?
each about 50nm in diameter, they store neurotransmitter
how big are secretory granules? and what do they contain?
about 100nm in diameter and contain soluble protein that appears dark in electron microscope, so sometimes called, dense-core vesicles
What is the membrane differentiations?
Dense accumulation of protein adjacent to and within the membranes on either side of the synaptic cleft
what is the active zones?
a specialized region of the presynaptic plasma membrane where synaptic vesicles dock and fuse. synaptic vesicles are clustered adjacent to the active zones
What is the postsynaptic density?
The protein thickly accumulated in and just under the postsynaptic membrane is called postsynaptic density. Contains neurotransmitter receptors
What is dendritic, axosomatic, axoaxonic, axospinous and dendrodendritic?
-name of different synapses
-axodendritic: postsynaptic membrane on a dendrite
-axosomatic: postsynaptic membrane on cell body
-axoaxonic: postsynaptic membrane on another axon
-axospinous: presynaptic axon contacts postsynaptic dendrite spine
-dendrodendritic: dendrites form synapse with another dendrite
What is Gray’s type I or asymmetrical synapses?
Synapses in which the membrane differentiation on postsynaptic side is thicker than that of presynaptic side (usually excitatory)
What is Gray’s type II or symmetrical synapses?
membrane differentiations are similar thickness on both pre- and post-synaptic membranes (usually inhibitory)
What are neuromuscular junctions?
chemical synapses between axons of motor neurons of spinal cord and skeletal muscle. fast and reliable. AP in motor axon causes an AP in muscle cell it innervates. one of largest synapses in body. pre synaptic terminal contains large number of active zones. postsynaptic membrane called the motor end-plate, contains a series of shallow folds
What are the 3 chemical categories of the major neurotransmitters?
amino acids, amines and peptides
What are the similarities and differences between amino acids, amines and peptides
-amino acids and amines are small organic molecules containing at least one nitrogen atom and stored and releases from synaptic vesicles
-peptide transmitters are large molecules, they’re chains of amino acids and stored in and released from secretory granules.
-secretory granules and synaptic vesicles often in same axon terminal therefore peptides often exist in same axon terminal as amines and amino acids
-small transmitters are synthesized in synaptic terminal and peptides are transported from the soma
What is considered slow and fast synaptic transmission?
slow: hundreds of milliseconds
fast: 10-100 msec
What are transporters? and their role
special proteins embedded in vesicles membrane, their job is concentrating amino acids and amines inside vesicle
How are peptides formed and stored in secretory granules?
-peptides formed when amino acids are strung together by ribosomes of cell body. occurs in rough ER and split in Golgi apparatus and one of the smaller peptide fragments is the active neurotransmitter
-secretory granules containing peptide transmitter bud off from Golgi apparatus and are carried to the axon terminal by axoplasmic transport
What triggers neurotransmitter release?
-triggered by arrival of AP in axon terminal. depolarisation of terminal membrane causes voltage-gated calcium channels in active zones to open. this elevation in calcium is the signal that causes neurotransmitter to be release from synaptic vesicle
What is the release of contents of vesicle?
called exocytosis, membrane of synaptic vesicle fuses to presynaptic membrane at active zone, allowing the contents of vesicle to spill into the synaptic cleft, can occur rapidly, within 0.2 msec of calcium influx. mouth of exocytotic fusion pore continues until membrane of vesicle fully incorporated into presynaptic membrane
What is endocytosis?
The vesicle membrane being recovered, particularly after exocytosis occurs, the recycled vesicle is refilled with neurotransmitter
What is the role of SNARE protein?
The specific binding and fusion of membranes depend on SNARE proteins. SNAREs allow one membrane to “snare” another
How does SNARE protein “snare” membranes?
Each SNARE peptide has a lipid-loving end that embeds itself within the membrane and a longer tail that projects into the outer membrane. Vesicles have “v-SNAREs” (like synaptobrevein) and the outer membrane has “t-SNAREs” (for target membrane, syntaxin and SNAP-25). The cytosolic types of SNAREs can bind very tightly to one another, allowing a vesicle to “dock” very closely to presynaptic membrane and nowhere else. a large array of other presynaptic proteins stick to this SNARE complex
What is synaptotagmin?
a v-SNARE, A vesicle protein and is the critical calcium sensor that rapidly triggers vesicles fusion and thus transmitter release
What is the general speed of release of peptides?
takes about 50msec or more
What are the 2 types of neurotransmitter receptors?
transmitter-gated ion channels and G-protein-coupled receptors
What are transmitter-gated ion channels made of?
They are membrane-spanning proteins consisting of 4 or 5 subunits that come together to form a pore between them
What happens when neurotransmitter binds to extracellular region of transmitter-gated ion channel?
induces conformational change, a slight twist of the subunits, which within microseconds causes pore to open, therefore ions can pass through
Describe the degree of selectivity of ions of transmitter-gated channels compared to voltage-gated channels.
Voltage-gated more selective than transmitter gated. nonetheless, as a rule if the open channels are permeable to Na+, the net effect will be to depolarise the postsynaptic cell from the resting membrane potential
What is an excitatory postsynaptic potential (EPSP)?
A transient postsynaptic membrane depolarisation caused by the presynaptic release of neurotransmitter
-synaptic activation of ACh-gated and glutamate-gated ion channels causes EPSPs
if the transmitter-gated channels are permeable to Cl-, what is the usual net effect of postsynaptic cell?
To hyperpolarise the postsynaptic cell from the resting membrane potential – it is inhibitory because it tends to bring the membrane potential away from threshold for generating action potentials
What is the inhibitory postsynaptic potential (IPSP)?
-A transient hyperpolarization of the postsynaptic membrane potential caused by the presynaptic release of neurotransmitter.
-synaptic activation of glyicine-gated or GABA-gated ion channels cause an IPSP
What are the steps of transmitter action for G-protein-coupled receptors? And compare their speed effect to chemical synaptic transmission
step 1.) neurotransmitter molecules bind to receptor proteins embedded in the postsynaptic membrane
step 2.) the receptor proteins activate small proteins, called G-proteins, which are free to move along the intracellular face of the postsynaptic membrane
step 3.) the activated g-protein activated “effector” proteins
-slower, longer lasting and much more diverse postsynaptic actions
What is the reversal potential on a I-V plot (I = current, V = voltage)?
The critical value at which the direction of current flow reverses
What can be effector proteins?
-G-protein-gated ion channels in membrane
-enzymes that synthesize molecules called second messengers that diffuse away in the cytosol
What can second messengers activate?
Additional enzymes in the cytosol that can regulate ion channel function and alter cellular metabolism
What are G-protein-coupled receptors often referred to and why?
metabotropic receptors, because they can trigger widespread metabolic effects
What effect does ACh have on heart compared to the skeletal muscles? And why?
-ACh slows rhythmic contractions of the heart by causing a slow hyperpolarization of the cardiac muscle cells
-In skeletal muscle ACh induces contraction by causing a rapid depolarisation of the muscle fibres.
-these difference actions are explained by the different receptors involved. –> in heart metabotropic Ach receptor is couple by G-protein to a K+ channel, therefore inhibitory effect / in skeletal muscle the receptor is a transmitter-gated ion channel permeable to Na+, therefore excitatory effect
What are autoreceptors?
-found on presynaptic axon terminal and are sensitive to the neurotransmitter release by the same presynaptic terminal
-typically G-protein-coupled receptors that stimulate second messenger formation
-common effect is inhibition of transmitter release, and sometimes transmitter synthesis
-allows for presynaptic terminal regulation, because can reduce release when concentration of transmitter around presynaptic terminal gets too high
what are the ways in which the synaptic cleft is cleared for another round of synaptic transmission?
-simple diffusion of transmitter though extracellular space and away from synapse
-often diffusion is aided by reuptake into the presynaptic axon terminal
-neurotransmitter action can also be terminated by enzymatic destruction in the synaptic cleft itself (example of this is ACh removal from neuromuscular junction, the enzyme acetylcholinesterase (AChE) is deposited in the cleft by muscle cells, AChE cleaves the ACh molecule, rendering it inactive at the ACh receptors ).
how does reuptake occur and what happens once reuptake has occured?
-reuptake occurs by action of specific transmitter transporter proteins located in the presynaptic membrane.
-once inside cytosol of terminal, transmitter may be reloaded into synaptic vesicles or enzymatically degraded and their constitute products recycled
neurotransmitter transporters do not exist in the membranes of glia surrounding the synapse, true or false?
False, they do exist and assist in removal of neurotransmitter from the cleft.
What is the importance of transmitter removal?
-too much transmitter for extended periods of time could lead to desensitisation
-for example, at the neuromuscular junction uninterrupted exposure to high concentrations of ACh after several seconds leads to desensitisation, in which despite the continued presence of ACH, the transmitter-gated channels close, this desensitised state can persist for many seconds even after the transmitter is removed
what is neuropharmacology?
the study of the effects of drugs of nervous system tissue
What is botulism and botulinum toxin?
-botulism is caused by several kinds of botulinum neurotoxins that are produced by the growth of C. botulinum in improperly canned foods.
-botulinum toxins are very potent blockers of neuromuscular transmission
-destroy certain SNARE proteins in the presynaptic terminals (which are critical for transmitter release) (so does tetanus toxin)
what does the block widow spider venom contain and what does it do?
-contains latrotoxin
-first increases ACh release and then eliminates the ACh release at the neuromuscular junction
What are inhibitor drugs?
One class of drug action which is to inhibit the normal function of specific proteins involved in synaptic transmission
What are receptor antagonists?
-inhibitors of the neurotransmitter receptors, binds to receptors and block (antagonize) the normal action of the transmitter.
-example of this is curare, arrow-tip poison used by native to paralyse prey. curare binds tightly to the ACh receptors in the skeletal muscle cells and blocks the actions of ACh, thereby preventing muscle contraction.
What are receptors agonists?
-Bind to receptors, mimic actions of naturally occurring neurotransmitter.
-example –> nicotine , derived from plant, binds to and activates ACh receptors in skeletal muscle, ACh receptors in CNS as well which are involved in the additive effects of tobacco use.
What is murphy’s law?
If a physiological process can go wrong, it will go wrong
what is synaptic integration?
Process by which multiple synaptic potentials combine within one postsynaptic neuron
What is the elementary unit of neurotransmitter release? And describe its significance
-contents of a single synaptic vesicle, vesicles each contain about the same number of transmitter molecules (several thousand), the total amount of transmitter release is some multiple of this number.
-amplitude of postsynaptic EPSP is some multiple of the response to the contents of a single vesicle –> aka postsynaptic EPSPs at a given synapse are quantised (multiples of an undividable unit, the quantum, reflects the number of postsynaptic receptors available at the synapse)
What is a miniature postsynaptic potential?
exocytosis of vesicles that occur at some low rate in the absence of presynaptic stimulation- often simply called mini
The amplitude of the postsynaptic EPSP evoked by the presynaptic action potential is a integer multiple of…?
The mini amplitude
What is quantal analysis?
A method of comparing the amplitudes of miniature and evoked PSPs, can be used to determine how many vesicles release neurotransmitter during normal synaptic transmission
quantal analysis of transmission at the neuromuscular junction reveals that a single action potential in the presynaptic terminal triggers how many synaptic vesicles? and compare this to the CNS synapses
-about 200 synaptic vesicles, causing an EPSP of about 40mV or more
-in CNS synapses, the contents of only a single vesicle are releases in response to a presynaptic action potential, causing an EPSP of only a few millivolt
What is EPSP summation?
represents the simplest form of synaptic integration in the CNS –> 2 types of summation, spatial and temporal
What is spatial summation?
the adding of EPSPs generated simultaneously at many different synapses on a dendrite (addition of EPSPs of many axons on same dendrite)
What is temporal summation?
the adding together of EPSPs generated at the same synapse if they occur in rapid succession, within about 1-15 msec of one another (addition of EPSPs of one axon firing multiple times)
What does the effectiveness of an excitatory synapse in triggering and action potential depend on?
-the distance the synapse is from the spike-initiation zone and on the properties of the dendritic membrane
As the current proceeds down the dendrite and farther from the synapse the EPSP amplitude will…
…dimmish because of the leakage of ionic current through membrane channels
What is the length constant?
An index of how far depolarisation can spread down a dendrite or axon, the longer the length constant the more likely it is that EPSPs generated at distant synapse will depolarise the membrane at the axon hillock. –> used in calculation at 37% of depolarisation at origin
What does the value of the length constant depend on in our idealised electrically passive dendrite?
1) the resistance to current flowing longitudinally down the dendrite, called the internal resistance (Ri)
2) the resistance to current flowing across the membrane called membrane resistance (Rm)
as length constant increase what happens to membrane resistance and why?
membrane resistance increases, because current will take the path of least resistance, and will flow down the inside of the dendrite rather than “leaking” out of membrane
What happens to length constant as internal resistance increases?
length constant will decrease, because more current will then flow across the membrane
does more current flow down wider or narrower dendrites and few or more membrane channels open?
Wider dendrites with fewer membrane channels open
What does internal resistance depend on?
-the diameter of dendrites
-electrical properties of cytoplasm
What does membrane resistance depend on?
number of open ion channels –> therefore length constant is not constant because different number of channels open and closed
What is the difference between inhibitory synapses and excitatory synapses?
-Bind different neurotransmitters at the transmitter-gated ion channels (GABA or glycine)
-they allow different ions to pass through their channels (e.g., Cl-)
What does opening a chloride channel allow?
Allows for Cl- to cross the membrane in direction that brings the membrane potential toward the chloride equilibrium potential, -65mV.
What is shunting inhibition?
the physical basis of this is the inward movement of negatively charged ions, which formally equivalent to the outward positive current flow
What does shunting inhibition act to reduce?
Rm (membrane resistance) and consequently length constant thus allowing current to flow across the membrane instead of internally down the dendrite to the spike initiation zone
what morphology does inhibitory synapses in the brain that use GABA or glycine as neurotransmitter have? and contrast with excitatory synapse that use glutamate
characteristic of Gray’s type II –> contrast with excitatory synapses that use glutamate, which have Gray’s type I
what is modulation?
synaptic activation of these receptors does not directly evoke EPSPs and IPSPs but instead modifies the effectiveness of EPSPs generated by other synapses with transmitter-gated channels
what are the mechanisms of neurotransmitter release?
-process of exocytosis stimulated by intracellular calcium
-proteins alter conformation - activated
-vesicle membrane incorporated into presynaptic membrane
-neurotransmitter released into cleft
-vesicle membrane recovered by endocytosis
What is the action of inhibitory synapses?
Take membrane potential away from action potential threshold
