neurophys3,4 spr 2018
This commit is contained in:
ackman678
@@ -131,6 +131,11 @@ Note:
|
||||
|
||||
Note:
|
||||
|
||||
TEA
|
||||
: tetraethylammonium
|
||||
: quaternary ammonium cation
|
||||
: blocks voltage gateed K+ channels
|
||||
|
||||
|
||||
---
|
||||
|
||||
@@ -309,29 +314,24 @@ others are ligand gated channels sensitive to chemical signals arising in the cy
|
||||
Note:
|
||||
|
||||
|
||||
|
||||
---
|
||||
|
||||
## If you have a gene for a channel, how do you determine its properties?
|
||||
|
||||
* Need an experimental system where you can express gene of interest functionally and away from other channels
|
||||
* Xenopus oocytes have been a historical way to do this
|
||||
|
||||
Note:
|
||||
|
||||
frog germ cells
|
||||
|
||||
---
|
||||
|
||||
## Xenopus oocytes
|
||||
|
||||
* Large (1 mm in diameter) cell that contains lots of protein synthesis machinery
|
||||
* Can inject RNA into it and it will express protein encoded by RNA
|
||||
* Works great for ion channels, can voltage clamp and determine properties of a given channel
|
||||
* Works great for expressing a gene of interest (ion channels!). Can voltage clamp and determine properties of a given channel
|
||||
* Can make specific mutations in genes and see what happens to function of protein
|
||||
|
||||
Note:
|
||||
|
||||
If you have a gene for a channel, how do you determine its properties?
|
||||
|
||||
frog germ cells
|
||||
|
||||
* Need an experimental system where you can express gene of interest functionally and away from other channels
|
||||
* Xenopus oocytes have been a historical way to do this
|
||||
|
||||
|
||||
---
|
||||
|
||||
@@ -339,7 +339,7 @@ Note:
|
||||
|
||||
Inject ion channel mRNA into oocyte ⟶ oocyte makes protein ⟶ patch clamp recordings
|
||||
|
||||
<figure><img src="figs/Neuroscience5e-Box-04C-0_cc95e56.jpg" height="400px"><figcaption>Neuroscience 5e Box 4C</figcaption></figure>
|
||||
<figure><img src="figs/Neuroscience5e-Box-04C-0_cc95e56.jpg" height="300px"><figcaption>Neuroscience 5e Box 4C</figcaption></figure>
|
||||
|
||||
Note:
|
||||
|
||||
@@ -347,7 +347,7 @@ shows voltage clamp experiment results after expression of a K channel in an ooc
|
||||
|
||||
---
|
||||
|
||||
## Diverse properties of K⁺ channels
|
||||
## Different K⁺ channels can have diverse properties
|
||||
|
||||
<div><img src="figs/Neuroscience5e-Fig-04.05-1R_copy_ff8f50a.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 4.5</figcaption></div>
|
||||
|
||||
@@ -408,9 +408,12 @@ We’ve learned from biophysical structure studies that in general ion channels
|
||||
|
||||
We can also guess a few characteristics of their structure from the classic voltage clamp and patch clamp studies we’ve discussed over the past couple classes…
|
||||
|
||||
from wikipedia:
|
||||
|
||||
>X-ray crystallography is a tool used for identifying the atomic and molecular structure of a crystal, in which the crystalline atoms cause a beam of incident X-rays to diffract into many specific directions. By measuring the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture of the density of electrons within the crystal. From this electron density, the mean positions of the atoms in the crystal can be determined, as well as their chemical bonds, their disorder and various other information.
|
||||
X-ray crystallography
|
||||
: tool for identifying the atomic and molecular structure of a crystal
|
||||
: crystalline atoms cause high energy (high frequency/short wavelength) electromagnetic waves (X-rays) to scatter in different directions
|
||||
: measure intensities and angles of the diffracted beams and compute a 3D model of the electron density in a crystal
|
||||
: information on mean atomic positions, type of chemical bonds, and more can be extracted
|
||||
|
||||
---
|
||||
|
||||
@@ -509,6 +512,8 @@ K | 0.27 | 0.46
|
||||
|
||||
Note:
|
||||
|
||||
remember water is a polar molecule. Has a net dipole moment of opposing charges in the hydrogen-oxygen bonds.
|
||||
|
||||
Larger cations cannot traverse the pore region, smaller cations like Na cannot enter the pore because the walls are just too far apart to stabilize a dehydrated Na ion long enough to pass through.
|
||||
|
||||
Na is the most hydrated ion with 4 to 6 water molecules in the first shell. Binds water strongly, making a stable hydration shell and moving together with the cation. Any sodium movement is followed by H2O movement (water retention, excretion).
|
||||
@@ -524,17 +529,17 @@ Na | 0.19 | 0.52
|
||||
K | 0.27 | 0.46
|
||||
|
||||
|
||||
[http://web-books.com/MoBio/Memory/Channel.htm :](http://web-books.com/MoBio/Memory/Channel.htm)
|
||||
a quote from [http://web-books.com/MoBio/Memory/Channel.htm](http://web-books.com/MoBio/Memory/Channel.htm):
|
||||
|
||||
>To pass through the potassium channel, an ion must remove most of its surrounding water molecules, leaving only two - one at the front and another at the back.
|
||||
|
||||
The selectivity filter of the sodium channel is slightly larger than that of the potassium channel. It may accommodate a Na⁺ ion attached with three water molecules, but not enough for a K⁺ ion attached with three water molecules.
|
||||
|
||||
|
||||
one more quote from [http://web-books.com/MoBio/Memory/Channel.htm](http://web-books.com/MoBio/Memory/Channel.htm):
|
||||
|
||||
>In the sodium channel, the Na⁺ ion is more permeable than the K⁺ ion. This is because the selectivity filter of the sodium channel is slightly larger than that of the potassium channel. It is large enough to accommodate a Na⁺ ion attached with three water molecules, but not enough for a K⁺ ion attached with three water molecules. Therefore, to pass through the sodium channel, the Na⁺ ion needs to remove only three, but the K⁺ ion has to remove four, water molecules from its first hydration shell. The required dehydration energy for the K⁺ ion is greater than the Na⁺ ion.
|
||||
|
||||
>In calcium channels, the permeability of monovalent cations (Na⁺ and K⁺) is about three orders of magnitude smaller than the Ca²⁺ permeability. This ion selectivity does not seem to involve hydration, because Ca²⁺ is more heavily hydrated than Na⁺, and the unhydrated diameters of Ca²⁺ and Na⁺ are almost identical. Then, how could calcium channels select Ca²⁺ over Na⁺?
|
||||
|
||||
>Although the permeability of monovalent cations in the calcium channel is quite small at normal ionic concentrations, large monovalent cationic current can be observed in the absence of Ca²⁺ and other divalent cations. This suggests that the calcium channel is basically permeable to both divalent and monovalent cations, but the selectivity arises from competition between ions. The calcium channel may contain a negatively charged binding site to facilitate ion conduction. The monovalent cations simply cannot compete with Ca²⁺ for this binding site. This idea has been confirmed experimentally. In the calcium channel, if a negatively charged glutamate residue in the pore-lining region is mutated into a positively charged lysine, the calcium channel becomes more permeable to Na⁺ than Ba2+
|
||||
|
||||
|
||||
@@ -665,7 +670,7 @@ Note:
|
||||
|
||||
Figure 21-13 Lodish 4th edition OR Figure 7-33 Lodish 5th edition. Structure and function of the voltage-gated Na⁺ channel.
|
||||
|
||||
[http://www.amazon.com/Molecular-Cell-Biology-Lodish/dp/0716776014](http://www.amazon.com/Molecular-Cell-Biology-Lodish/dp/0716776014)
|
||||
<!--[http://www.amazon.com/Molecular-Cell-Biology-Lodish/dp/0716776014](http://www.amazon.com/Molecular-Cell-Biology-Lodish/dp/0716776014) -->
|
||||
|
||||
<!-- Sodium channel inactivation
|
||||
|
||||
@@ -749,7 +754,7 @@ myotonia: muscle contraction
|
||||
|
||||
|
||||
|
||||
---
|
||||
--
|
||||
|
||||
## Diseases caused by altered ion channels
|
||||
|
||||
@@ -779,7 +784,7 @@ amblyopia: greek for ‘blunt vision’, decr vision through an eye because of a
|
||||
|
||||
|
||||
|
||||
---
|
||||
--
|
||||
|
||||
## Diseases caused by altered ion channels
|
||||
|
||||
@@ -800,7 +805,7 @@ Paralysis: muscle weakness
|
||||
Note:
|
||||
|
||||
|
||||
---
|
||||
--
|
||||
|
||||
## Epilepsy can result from mutated Na⁺ channels
|
||||
|
||||
@@ -841,14 +846,12 @@ GEFS: generalized epilepsy with febrile seizures
|
||||
|
||||
Note:
|
||||
|
||||
Lastly let's remind ourselves of the importance of ion transporters in maintaining the concentration gradients across the nerve cell membrane. We've previously discussed the active transporter the Na/K pump that is crucial for maintaining Na/K gradients but there are others that maintain gradients for other physiologically relevant ions like Cl, Ca. Remember these transporters are all very slow compared to ion channels, requiring several milliseconds to move a few ions compared to thousands of ions per second conducted across the membrane for an ion channel.
|
||||
|
||||
Ouabain, plant 'arrow' poison traditionally from africa from the Acokanthera schimperi and Strophanthus gratus plants
|
||||
Lastly let's remind ourselves of the importance of ion transporters in maintaining the concentration gradients across the nerve cell membrane. We've previously discussed the active transporter the Na/K pump that is crucial for maintaining Na/K gradients but there are others that maintain gradients for other physiologically relevant ions like Cl, Ca.
|
||||
|
||||
Remember these transporters are all very slow compared to ion channels, **requiring several milliseconds to move a few ions** compared to **thousands of ions per second** conducted across the membrane for an ion channel.
|
||||
|
||||
<!-- ## Na⁺/K⁺ pump video
|
||||
|
||||
<div><video height=400px controls src="figs/Animation04-02TheSodiumPotassiumPump.mp4"></video><figcaption>Neuroscience 5e Animation 4.2</figcaption></div>
|
||||
-->
|
||||
<div><video height=400px controls src="figs/Animation04-02TheSodiumPotassiumPump.mp4"></video><figcaption>Neuroscience 5e Animation 4.2</figcaption></div> -->
|
||||
|
||||
---
|
||||
Ouabain, plant 'arrow' poison traditionally from africa from the Acokanthera schimperi and Strophanthus gratus plants. Binds to the Na+/K+ pump. Cardiac dysfunction ensues.
|
||||
|
||||
@@ -21,11 +21,11 @@ and electrical...
|
||||
|
||||
---
|
||||
|
||||
## Electrical and chemical synapses differ in their transmission mechanisms
|
||||
## Electrical and chemical synapses have different mechanisms for transmission
|
||||
|
||||
<div><figcaption class="big">chemical synapse</figcaption><img src="figs/Neuroscience5e-Box-5A-1_c61ef03.jpg" height="200px"><figcaption>Neuroscience Box 5A</figcaption></div>
|
||||
<div class="fragment fade-in" data-fragment-index="1"><figcaption class="big">electrical synapse</figcaption><img src="figs/Neuroscience5e-Fig-05.01-1R_4f24cb4.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 5.1</figcaption></div>
|
||||
<div class="fragment fade-in" data-fragment-index="1"><figcaption class="big">electrical synapse</figcaption><img src="figs/Neuroscience5e-Fig-05-01b_5112455.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 5.1</figcaption></div>
|
||||
<div><figcaption class="big">chemical synapse</figcaption><img src="figs/Neuroscience5e-Box-5A-1_c61ef03.jpg" height="250px"><figcaption>Neuroscience Box 5A</figcaption></div>
|
||||
<div class="fragment fade-in" data-fragment-index="1"><figcaption class="big">electrical synapse</figcaption><img src="figs/Neuroscience5e-Fig-05.01-1R_4f24cb4.jpg" height="250px"><figcaption>Neuroscience 5e Fig. 5.1</figcaption></div>
|
||||
<div class="fragment fade-in" data-fragment-index="1"><figcaption class="big">electrical synapse</figcaption><img src="figs/Neuroscience5e-Fig-05-01b_5112455.jpg" height="250px"><figcaption>Neuroscience 5e Fig. 5.1</figcaption></div>
|
||||
|
||||
|
||||
Note:
|
||||
@@ -105,6 +105,8 @@ quadrillion synapses, 10^15 in our nervous system
|
||||
|
||||
important in diseases of pathological oscillations/synchrony like childhood epilepsy, etc
|
||||
|
||||
Electrical synapses and synchronization characterisitc of cells that stimulate pulses of pituitary hormones (e.g oxytocin/vasopressin secretion).
|
||||
|
||||
---
|
||||
|
||||
## Chemical synapses
|
||||
@@ -121,43 +123,19 @@ Note:
|
||||
|
||||
## Synapse structure as seen by electron microscopy
|
||||
|
||||
<div><figcaption class="big">chemical synapse, type 1</figcaption><img src="figs/image2_1bf4990.png" height="200px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
<div><figcaption class="big">chemical synapse, type 1</figcaption><img src="figs/image2_1bf4990.png" height="220px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
|
||||
<div><figcaption class="big">chemical synapse, type 2</figcaption><img src="figs/image3_5af29bc.png" height="200px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
<div><figcaption class="big">chemical synapse, type 2</figcaption><img src="figs/image3_5af29bc.png" height="220px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
|
||||
<div><figcaption class="big">synaptic vesicles</figcaption><img src="figs/image4_b39a9f7.png" height="200px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
<div><figcaption class="big">synaptic vesicles</figcaption><img src="figs/image4_b39a9f7.png" height="220px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
|
||||
<div><figcaption class="big">synaptic cleft</figcaption><img src="figs/image5_a67adf4.png" height="200px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
<div><figcaption class="big">synaptic cleft</figcaption><img src="figs/image5_a67adf4.png" height="220px"><figcaption>[SynapseWeb, Kristen M. Harris, PI](https://synapseweb.clm.utexas.edu)</figcaption></div>
|
||||
|
||||
Note:
|
||||
|
||||
* synapse, Gray type 1 is asymmetrical synapse. Usually excitatory synapse. Spherical vesicles.
|
||||
* synapse, Gray type 2 is symmetrical synapse. Usually inhibitory synapse. Elongated vesicles.
|
||||
|
||||
---
|
||||
|
||||
## 11 steps of synaptic transmission
|
||||
|
||||
<div style="font-size:0.8.em">
|
||||
<div></div>
|
||||
|
||||
1. Neurotransmitter is synthesized and packaged into vesicles
|
||||
1. An action potential invades the presynaptic terminal
|
||||
1. Depolarization causes opening of voltage-gated calcium channels
|
||||
1. There is a rapid influx of Ca²⁺. 1000x concentration difference across the membrane(1x10⁻⁴ mM inside, 1 mM outside)
|
||||
1. Calcium causes vesicles to fuse with membrane
|
||||
1. Neurotransmitter is released into cleft
|
||||
1. Transmitter binds to receptors on postsynaptic cell
|
||||
1. This opens or closes postsynaptic channels
|
||||
1. Postsynaptic current flows inside post-synaptic cell
|
||||
1. Removal of neurotransmitter by glia uptake or enzymatic degradation
|
||||
1. Retrieval of membrane via endocytosis
|
||||
|
||||
</div>
|
||||
|
||||
Note:
|
||||
|
||||
|
||||
---
|
||||
|
||||
## Synaptic transmission
|
||||
@@ -177,6 +155,30 @@ Note:
|
||||
* The neurotransmitter is inactivated and/or removed from the synaptic cleft (active transport into presynaptic neuron or glial cells or both)
|
||||
* The vesicular membrane is recovered by endocytosis and recycled
|
||||
|
||||
---
|
||||
|
||||
## 11 steps of synaptic transmission
|
||||
|
||||
<div style="font-size:0.8em;">
|
||||
<div></div>
|
||||
|
||||
1. **Neurotransmitter synthesized** and/or packaged into vesicles
|
||||
1. **Action potential** enters the presynaptic terminal
|
||||
1. **Voltage-gated calcium channels** open because of depolarization
|
||||
1. **Calcium influx** occurs rapidly. Ca²⁺ concentration difference is 1000x across the cell membrane
|
||||
1. **Vesicles fuse** with membrane because of calcium flux
|
||||
1. **Neurotransmitter release** into synaptic cleft
|
||||
1. **Neuroransmitter binds** to receptors on postsynaptic cell
|
||||
1. **Postsynaptic ion channels** open or close
|
||||
1. **Postsynaptic current** flux occurs across post-synaptic cell membrane
|
||||
1. **Neurotransmitter removed** from synaptic cleft by enzymatic degradation or glial cell uptake
|
||||
1. **Vesicle membrane** recycled via endocytosis
|
||||
|
||||
</div>
|
||||
|
||||
Note:
|
||||
|
||||
|
||||
---
|
||||
|
||||
|
||||
@@ -220,6 +222,8 @@ The vagus nerve supplies motor parasympathetic fibers to all the organs except t
|
||||
|
||||
Note:
|
||||
|
||||
Otto Loewi, 1921
|
||||
|
||||
Free acetylcholine acts on **muscarinic receptors** which **hyperpolarize** the cells of the SA node and slow the conduction of the action potential through the AV node. This slows heart rate. Acetylcholine also decreases Ca2+ influx which lowers the heart's force of contraction.
|
||||
|
||||
--
|
||||
@@ -242,14 +246,14 @@ Note:
|
||||
|
||||
## Acetylcholine (ACh) shown to be the vagus factor
|
||||
|
||||
<div style="font-size:0.8em;">
|
||||
<div></div>
|
||||
|
||||
* Sir Henry Dale purified ACh (1914) and showed that it is vagus nerve substance
|
||||
* Can apply ACh to muscle and evoke an end plate potential (EPP)
|
||||
* ACh action has same pharmacology as vagus nerve substance in that it is sensitive to curare (a plant poison that kills by preventing muscle contraction). Competes with curare for receptor binding
|
||||
* Henry Dale and Otto Loewi shared Nobel prize (1936):
|
||||
|
||||
<div style="font-size:0.7em;">
|
||||
<div></div>
|
||||
|
||||
>"for their discoveries relating to chemical transmission of nerve impulses"
|
||||
|
||||
</div>
|
||||
@@ -319,7 +323,7 @@ Note:
|
||||
|
||||
How have we come to learn about the properties of chemical synaptic transmission?
|
||||
|
||||
---
|
||||
<!--
|
||||
|
||||
## Neuromuscular junction
|
||||
|
||||
@@ -327,11 +331,9 @@ How have we come to learn about the properties of chemical synaptic transmission
|
||||
|
||||
<div><img src="figs/image11_5a29be3.png" height="200px"><figcaption></figcaption></div>
|
||||
|
||||
Note:
|
||||
|
||||
motor unit is a motor neuron’s axon terminals and all the skeletal muscle fibers it innervates (10 for extraocular muscles, 1000 for thigh muscles). Motor pool is a bunch of motor units of same fiber type.
|
||||
|
||||
---
|
||||
|
||||
|
||||
## Muscle action potentials
|
||||
|
||||
@@ -341,11 +343,6 @@ motor unit is a motor neuron’s axon terminals and all the skeletal muscle fibe
|
||||
<figure><img src="figs/endplate-muscle-AP_copy_3914f33.jpg" height="200px"><figcaption></figcaption></figure>
|
||||
|
||||
|
||||
Note:
|
||||
|
||||
|
||||
--
|
||||
|
||||
## Muscle action potentials
|
||||
|
||||
* Recordings in the junction reveal local potential changes at the end plate before a regenerative action potential is produced
|
||||
@@ -353,27 +350,20 @@ Note:
|
||||
<figure><img src="figs/endplate-potential-muscle-AP_copy_3befd61.jpg" height="200px"><figcaption></figcaption></figure>
|
||||
|
||||
|
||||
Note:
|
||||
|
||||
--
|
||||
|
||||
## Muscle action potentials
|
||||
|
||||
* These local potentials are called end plate potentials (EPPs)
|
||||
* End plate potentials are generated **at the end plate**
|
||||
|
||||
<figure><img src="figs/endplate-potential-muscle-AP-curare_copy_6afd350.jpg" height="200px"><figcaption></figcaption></figure>
|
||||
|
||||
|
||||
Note:
|
||||
|
||||
-->
|
||||
|
||||
|
||||
---
|
||||
|
||||
## End plate potential
|
||||
|
||||
A presynaptic action potential releases a lot of ACh, opening channels in the muscle cell. The resulting depolarization is called an end plate potential (EPP).
|
||||
A presynaptic action potential releases a lot of ACh, opening channels in the muscle cell. The resulting depolarization in the muscle cell at the neuromuscular junction is called an end plate potential (EPP).
|
||||
|
||||
<div><img src="figs/Neuroscience5e-Fig-05.06-1R_copy_c01be61.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.6</figcaption></div>
|
||||
|
||||
@@ -382,7 +372,13 @@ A presynaptic action potential releases a lot of ACh, opening channels in the mu
|
||||
|
||||
Note:
|
||||
|
||||
End plate potentials evoked by motor neuron stimulation almost are almost always above threshold and result in an action potential along the muscle fiber
|
||||
Muscle fibers are excitable cells. They are multinucleated myocytes. They too generate action potentials.
|
||||
|
||||
End plate potentials evoked by motor neuron stimulation almost are almost always above threshold and result in an action potential along the muscle fiber.
|
||||
|
||||
It is the synaptic potential at the neuromuscular junction.
|
||||
|
||||
motor unit is a motor neuron’s axon terminals and all the skeletal muscle fibers it innervates (10 for extraocular muscles, 1000 for thigh muscles). Motor pool is a bunch of motor units of same fiber type.
|
||||
|
||||
---
|
||||
|
||||
@@ -413,11 +409,20 @@ Note:
|
||||
|
||||
## Quantal neurotransmission
|
||||
|
||||
* By lowering Ca²⁺ one can reduce the amount of transmitter released by an AP
|
||||
* Here [Ca²⁺] is so low that *many* presynaptic APs fail to release any ACh
|
||||
* Other APs release 1 to 6 quanta
|
||||
<div style="width:350px; float:left; font-size:0.7em;">
|
||||
<div></div>
|
||||
|
||||
<figure><img src="figs/Neuroscience5e-Fig-05.07-1R_copy_dd645da.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.7</figcaption></figure>
|
||||
* Lowering [Ca²⁺] reduces the amount of total transmitter (no. of vesicles) released by an AP
|
||||
* Here [Ca²⁺] is so low that *often* presynaptic APs fail to release any ACh. But sometimes APs will release 1 to 6 quanta
|
||||
* The distribution of stimulated EPPs in low [Ca²⁺] has multiple modes (several local maxima). Multiples of the smallest EPP amplitude (e.g. 0.4 mV)
|
||||
|
||||
</div>
|
||||
|
||||
<figure style="width:550px; margin:0 25px; float:left;">
|
||||
<figcaption class="big">Histogram of EPP amplitudes in low [Ca<sup>2+</sup>]</figcaption>
|
||||
<img src="figs/Neuroscience5e-Fig-05.07-1R_copy_dd645da.jpg" height="400px">
|
||||
<figcaption>Neuroscience 5e Fig. 5.7</figcaption>
|
||||
</figure>
|
||||
|
||||
|
||||
Note:
|
||||
@@ -432,7 +437,7 @@ If you measure the amplitudes of these small low calcium EPPs and plot their dis
|
||||
|
||||
* The **MEPP is the quantal event of neurotransmission**. It represents the postsynaptic response to the release of a single vesicle of neurotransmitter
|
||||
* The EPP is the result of the synchronized release of many vesicles. It is the sum of many MEPPs
|
||||
* Bernard Katz Nobel prize (1970)
|
||||
* Bernard Katz, Nobel prize (1970)
|
||||
|
||||
<figure><img src="figs/image12_0957581.png" height="100px"><figcaption>Bernard Katz</figcaption></figure>
|
||||
|
||||
@@ -503,9 +508,9 @@ Note:
|
||||
|
||||
--
|
||||
|
||||
## The role of Ca²⁺
|
||||
## The role of calcium
|
||||
|
||||
<div style="font-size:0.8em; margin:25px 0;">
|
||||
<div style="width: 400px; float:left; font-size:0.7em;">
|
||||
<div></div>
|
||||
|
||||
* If extracellular Ca²⁺ is removed or Ca²⁺ entry is blocked, there will be no release
|
||||
@@ -513,7 +518,14 @@ Note:
|
||||
|
||||
</div>
|
||||
|
||||
<div><figcaption class="big">Voltage-clamp presynaptic neuron and block Na⁺/K⁺ currents with TTX/TEA</figcaption><img src="figs/Neuroscience5e-Fig-05.10-0_copy_a76faf6.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 5.10</figcaption></div>
|
||||
<div style="width: 450px; float:left; margin: 0 25px">
|
||||
<figcaption class="big">
|
||||
|
||||
Voltage-clamp presynaptic neuron and
|
||||
block Na⁺/K⁺ currents with TTX/TEA
|
||||
|
||||
</figcaption>
|
||||
<img src="figs/Neuroscience5e-Fig-05.10-0_copy_a76faf6.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 5.10</figcaption></div>
|
||||
|
||||
|
||||
Note:
|
||||
@@ -523,9 +535,9 @@ Note:
|
||||
|
||||
--
|
||||
|
||||
## The role of Ca²⁺
|
||||
## The role of calcium
|
||||
|
||||
<div style="font-size:0.8em; margin:25px 0;">
|
||||
<div style="font-size:0.7em; margin:25px 0;">
|
||||
<div></div>
|
||||
|
||||
* Intracellular injection of Ca²⁺ into the presynaptic terminal will stimulate release
|
||||
@@ -533,8 +545,9 @@ Note:
|
||||
|
||||
</div>
|
||||
|
||||
<div><figcaption class="big">microinjection of Ca²⁺ into presynaptic terminal</figcaption><img src="figs/Neuroscience5e-Fig-05.11-2R_copy_13a54e8.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.11</figcaption></div>
|
||||
<div><figcaption class="big">microinjection of Ca²⁺ chelator BAPTA into presynaptic terminal</figcaption><img src="figs/Neuroscience5e-Fig-05.11-3R_copy_6d4bfd9.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.11</figcaption></div>
|
||||
<div style="width:400px; float:left"><figcaption class="big">microinjection of Ca²⁺ into presynaptic terminal</figcaption><img src="figs/Neuroscience5e-Fig-05.11-2R_copy_13a54e8.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.11</figcaption></div>
|
||||
|
||||
<div style="width:450px; float:left; margin: 0 25px"><figcaption class="big">microinjection of Ca²⁺ chelator BAPTA into presynaptic terminal</figcaption><img src="figs/Neuroscience5e-Fig-05.11-3R_copy_6d4bfd9.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.11</figcaption></div>
|
||||
|
||||
|
||||
Note:
|
||||
@@ -548,7 +561,7 @@ Note:
|
||||
|
||||
---
|
||||
|
||||
## There are lots of proteins involved in synaptic vesicle cycling
|
||||
## Many proteins are involved in synaptic vesicle cycling
|
||||
|
||||
* Many specific proteins have been isolated from presynaptic terminals
|
||||
* Some of these proteins are required for different steps of vesicle cycling: budding, docking, priming, fusion
|
||||
@@ -583,7 +596,7 @@ Model after Takamori et al 2006
|
||||
|
||||
Note:
|
||||
|
||||
NSF: ATPase NSF important for fusion of vesicle with membranes of the golgi apparatus. NEM senstivie fusion protein.
|
||||
NSF: ATPase NSF important for fusion of vesicle with membranes of the golgi apparatus. NEM sensitive fusion protein.
|
||||
|
||||
snaps: soluble NSF-attachment proteins
|
||||
|
||||
@@ -595,17 +608,26 @@ Model after Takamori et al 2006
|
||||
|
||||
## Molecular mechanisms of synaptic vesicle exocytosis
|
||||
|
||||
<div style="width: 400px; float:left; font-size:0.7em">
|
||||
<div></div>
|
||||
|
||||
* SNARES ('SNAP' receptors) tether the vesicle to plasma membrane
|
||||
* SNAP-25 is a plasma membrane SNARE that regulates the assembly of two other SNAREs
|
||||
* Syntaxin is a plasma membrane SNARE
|
||||
* Synaptobrevin is a vesicle SNARE
|
||||
* Together they tether the vesicle to the plasma membrane
|
||||
* Synaptotagmin is a vesicle Ca²⁺ sensor and helps trigger vesicle fusion
|
||||
|
||||
<figure><figcaption class="big">Vesicle bound to plasma membrane</figcaption><img src="figs/Neuroscience5e-Fig-05.14-1R_copy_6de21e5.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 5.14</figcaption></figure>
|
||||
</div>
|
||||
|
||||
<div style="width: 450px; float:left; margin: 0 25px;"><figcaption class="big">Vesicle bound to plasma membrane</figcaption><img src="figs/Neuroscience5e-Fig-05.14-1R_copy_6de21e5.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 5.14</figcaption></div>
|
||||
|
||||
|
||||
Note:
|
||||
|
||||
|
||||
Many proteins specific to presynaptic terminals have been isolated.
|
||||
These proteins are required for different steps of vesicle cycling: budding, docking, priming, fusion.
|
||||
|
||||
NSF
|
||||
: NEM-sensitive fusion protein (orig found to be important for fusion of vesicles with membranes of Golgi apparatus)
|
||||
: ATPase
|
||||
@@ -643,9 +665,7 @@ Note:
|
||||
|
||||
>Cleavage of the SNARE proteins inhibits release of acetylcholine.[45] Hence, botulinum toxins A, B, and E specifically cleave SNAREs, preventing "neurosecretory vesicles" from docking/fusing with the interior surface of the plasma membrane of the nerve synapse, and so block release of neurotransmitter. In inhibiting acetylcholine release, nerve impulses are blocked, causing the flaccid (sagging) paralysis of muscles characteristic of botulism[45]
|
||||
|
||||
|
||||
|
||||
---
|
||||
--
|
||||
|
||||
## Synaptic vesicle toxins
|
||||
|
||||
@@ -668,7 +688,7 @@ SNARES
|
||||
|
||||
|
||||
|
||||
---
|
||||
--
|
||||
|
||||
## Botox
|
||||
|
||||
@@ -683,6 +703,7 @@ Note:
|
||||
when botox is injected in small amounts, it can effectively weaken a muscle for a period of three to four months
|
||||
|
||||
|
||||
|
||||
---
|
||||
|
||||
## Synaptic transmission summary video
|
||||
@@ -693,14 +714,9 @@ Note:
|
||||
|
||||
---
|
||||
|
||||
## Midterm thursday
|
||||
## Midterm tuesday
|
||||
|
||||
* Similar format as the practice midterm
|
||||
* 100 points total, 25% of your grade.
|
||||
* 100 points total, 25% of your grade
|
||||
* Covers material in lectures 1–6
|
||||
* today's material covers Chapter 5, pages 77-95
|
||||
* Hannah's office hrs this week: Wednesday 3:30 – 5:30pm Biomed 101
|
||||
|
||||
Note:
|
||||
|
||||
---
|
||||
* James' extra office hrs this week: Friday 1:30 – 3:30pm Biomed 101
|
||||
|
||||
Reference in New Issue
Block a user