Synaptic Transmission Basics Flashcards
Describe gap junctions?
Low resistance connections and rapid communication. At gap junctions the two cells are separated by only 3 nm. This narrow gad is spanned by a cluster of 20 different proteins called connexins. 6 connexins combine to form a subunit called a connexons. Two two hemi-channels (connexons) on in each membrane meet to form a gap junction. Energy can flow both ways in gap junctions.
What does it mean that cells at gap junctions are electrically coupled?
Current (in the form of ions) pass through gap junctions which are created by two connecting connexons are said to be energetically coupled.
Where are electrical synapses common?
Every part of the mammalian CNS
What are postsynaptic potentials (PSP) created?
When neurons are energetically couples at the gap junction, a small amount of ionic current flows across the gap junction into the other neuron this causes an electrically mediated post-synaptic potential in the second neuron.
What does is the impact of electrical synapses being bi-directional?
When an AP is generated in the second neuron, it will produce a PSP in the first neuron.
How strong is the PSP generated by one neuron?
1mV. However, one neuron usually has electrical synapses with many other neurons, so several PSPs occurring simultaneously could be enough to strongly excite a neurons
When are gap junctions most common?
Early development
Name a type of response that gap junctions frequently mediate?
Escape responses. This is because they are so fast! Passive current flow across the gap junction is virtually instantaneous.
How wide is the synaptic cleft?
20-25nm wide. This is 10x the width of the gap junction. The synaptic cleft is filled with fiberous proteins
How do electrical currents flow from one electrical synapse to another?
Connexons on the upstream neuron are precisely aligned to connexons of the downstream neuron at the gap junction. Said another way, six presynaptic connexons align with six post-synaptic connexons to form pores that connect the cells.
What is larger, the pore of a connexon or the pore of a voltage-gated ion channel?
The pore of a connexon. As a result many substances diffuse between the gap junctions of the pre and post synaptic neurons. In fact in addition to ions, molecules with molecular weights as great at several hundred daltons can diffuse through the gap junction. This mean that ATP and other important intracellular metabolites, as second messenger
What are connexons made of?
Connexins. There are several different types of connexins that yield gap junctions with different physiological properties.
How do electrical synapses work?
ionic current flows passively from one neuron to another. The source of this current is typically the pre-synaptic action potential.
Are electrical synapses bidirectional?
Yes! Although some a uni-directional
What does to mean that electrical transmission is graded?
It can occur below action potential threshold and can be hyper-polarizing or depolarizing?
How is it that electrical synapses can he hyper-polarizing or depolarizing?
not sure?
Describe the connexin and connexon protein structure?
It is a single protein that passes through the membrane four times. So it is called a 4-pass transmembrane protein. It takes six of these proteins to form 1 connexon. Connexons have closed and open configurations regulated, which are regulated by Ca2+, pH and voltage
How is ion movement through connexons facilitated?
By polar residues lining the pore.
Why are electrically coupled synapses so fast?
Low resistance of the connection
What are the primary factors that determine input resistance Rin?
Size and myelination. Larger cells have lower re
Do networks of energetically coupled neurons tend to exhibit higher or lower and what impact doe this have on current required to depolarize them to threshold?
Due to increased membrane surface area, networks of coupled neurons tend to have low resistance, which means that a greater current is required for an AP. This reduces the sensitivity of some electrically coupled synapses such that they require synchronous firing form many pre-synaptic neurons in order to generate a threshold depolarization.
Is more or less current required to achieve depolarization in electrically coupled cells as opposed to chemical cells?
Using deltaV=delta I * Rin
v=voltage across the membrane
I=current
Rin=in put resistance, which is the inverse of conductance.
We therefore know, it depends on the size of the post-synaptic neuron. If it is a small post-synaptic neuron resistance will be high (because there are few channels) therefore a low current will be required for depolarization. This is the case for the tail flip of the crayfish. This tail flip is an escape response. Since the post-synaptic neuron is small, only a small current is required for it to depolarize it.
Conversely, the motor neuron that cause the inking response of the Aplasia (sea slug), need the synchronous firing of many presynaptic cell because their large surface area lowers the resistance of the post synaptic neuron meaning that it needs a large depolarization current I, to reach threshold for an AP to fire.
Name two diseases that gap junctions are implicated in?
Charcot-Marie-Tooth Disease: Demyelination due to mutations of a Schwann cell connexin (connexin 32). Schwann cell death results in deformation due to imbalance of opposing muscle performance.
A leading cause of hereditary deafness: Caused by mutations leading to loss of connexin 26 in cochlear epithelial cells.
Discuss the role of gap junctions.
Found in all cell types and organs and plays a role in development and structural integrity.
At the synapse:
Permits rapid times and is thus key in escape response
Connects groups of cells for synchronicity
Width allows them to transfer metabolites (cAMP, IP3, small peptides, myelination)
Glial cells connect via gap junctions into large network
Describe the importance of the synchronization of neuronal activity that is possible through energetic coupling?
A single electrical pre-synaptic neuron can energetically couple with many post-synaptic neurons thereby creating synchronized activity. For example, brainstem neurons that generate the rhythmic electrical activity that underlies breathing are electrically coupled.
I am still not entirely clear on how the allow for synchronization. Something about a large network of simultaneously firing cells.
What is the space between chemical synapses called?
The synaptic cleft
What happens when calcium enters the pre-synaptic cell?
The transient increase in Ca concentration, allows the NT vesicles to fuse with the pre-synaptic membrane and release their contents into the synaptic cleft.
What happens when the NT diffuses across the post-synaptic cleft?
They bind to specific receptors, which causes channels in the post-synaptic membrane to open or sometimes to close. This changes the ability of ions to flow into or out of the post-synaptic cell.
This NT induced current flow alters conductance and usually membrane potential of the post-synatpic neuron. This change in membrane potential then changes the likelihood of a neuron firing an AP.
How is NT removed from the synaptic cleft?
It is taken up by glial cells or degraded by enzymatic degradation. If this NT remained in the cleft, the action of the AP would continue.
How many NT have been identified?
More than 100. They are broadly classified as small molecule neuropeptides and neurotransmitters
Do neurons produce more than one type of neuronal transmitters?
Until recently it was believed that neurons produced only one type of neurotransmitter, but there is evidence that some neurons produce two or more neurotransmitters When more than one transmitter is released by a neuron these neurons are called co-transmitters.
Where are small molecule NT manufactured?
In the pre-synaptic terminal. The enzymes need to make these NTs are made in the neuronal cell body and then transported to the nerve terminal by slow axonal transport. The precursor materials need to make these NT are pulled into the terminal form the extra cellular space.
What are small clear-core vesicles?
Most small-molecule NTs are are packaged into vesicles that are 40-60nm in diameter, the centers of these vesicles appear clear on an electonmicrograph, accordingly these vesicles are referred to as small-clear core vesicles.
What defines neuropeptides?
They are synthesized in the cell body of a neuron. As such it is produced a long-way from its secretion site. It is brought to the terminal via fast axonal transport. Because these vesicles are electon dense they are often referred to as large dense-core vesicles.
Where is he neuromuscular junction?
The between the spinal motor neurons and the skeletal muscles. Visualize the connection of the spinal chord to the skeletal muscle.
What are end plates?
The synapse that the neuromuscular junction.
What is end plate potential (EPP)
It is the change membrane potential across the end plate at the neuromuscular junction.
Said another way EPP is the depolarization of a muscle neuron that occurs when the pre-synaptic motor neuron fires an AP. Moreover, EPPs are evoked by the stimulation of the pre-synaptic motor neuron. This usually causes a sufficient depolarization in the post-synaptic muscle cell to produce an action potential.
What is an MEPP?
A miniature EPP. They are spontaneous and occur in the absence of pre-synaptic stimulation. MEPPs are 1mV and EPPs tend to be over 50 mV.
What happens if the neuromuscular junction is bathed in a solution that has a low concentration of Ca?
The post-synaptic muscle cell produces sub-threshold EPPs that are to sufficient to depolarize the cell and cause a contraction. In fact, they are about the same size as MEPPs. This tells us that no matter how little Ca there is in the extra cellular fluid interfering with the fusion and release of pre-synaptic vesicles, at least enough NT released to cause an MEPP change in potential. Moreover, it is not possible to release an amount of NT less than what is required to cause a random MEPP.
What is the quantal nature of NT release?
The NTs are released from the pre-synaptic neuron tend to occur multiples of a specific amount. Moreover, it is quantal. One of the ways that we know this is that EPP amplitude tends to occur as integer multiples of the mean MEPP amplitude.
Moreover, a repsonse to a neurotransmitter either happens in a certain amount or a multiple of that amount or it does’t happen at all.
What is the significance of the quantal natures of NTs?
Realizing this led to the understand of vesicular transport of NT. These vesicles are what create this quantal nature.
How many molecules of Ach are present in a single vesicle?
10,000. Interestingly this number corresponds very well to the amount of Ach required for an MEPP. This, of course, supports the idea that these quanta arise of the discharge of the contents of a single vesicle of Ach
What toxin do puffer fish produce and what does it do?
They produce TTX and it blocks all sodium channels
What is the drug 4-amino pyridine or 4-AP?
Increases the number of quanta released by a single action potential. It works by blocking K+ channels to prevent the repolarization of the cell. Varying the amount of 4-AP applied to the presynaptic cells
How was it proven that each vesicle that fused whit he presynaptic membrane was responsible for a single quata?
John Heuser among others correlated vesicle fusion with the number of quanta (MEPPs) in post-synaptic cell. They treated the presynaptic cell with 4-AP in order to increase the release of quanta. They then used the electron microscopy to count the vesicle fusion. They were abel to draw an entirely linear correlation between the number of quanta released and the number of vesicles fussing.
What is a quanta?
The amplitude in mV created by one MEPP. Now we know that a quanta is the amount of EPP created by the release of one NT vesicle, at the time that was not understood and each unit of potential neurotransmitter. IN a sense they were equivalent to MEPPs.
How is the fusion of NT vesicles with the presynaptic membrane visualized?
With an electron microscopical technique called freeze-fracture microscopy.
What is endocytosis?
The process by which fused vesicles are taken back into the cytoplasm of the nerve terminal.
What happened to capacitance when synaptic vesicles fuse the pre-synaptic terminal during NT release?
The membrane capacitance (Cm) increases because capacitance is proportional to surface area
