neurophys3,4 spr 2018

2018-04-19 10:18:29 -07:00
parent 758155b50c
commit c675c3eecc
2 changed files with 135 additions and 116 deletions
--- a/neurophysiology3.md
+++ b/neurophysiology3.md
@@ -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.