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neurophysiology3.md
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@@ -15,7 +15,7 @@ Note:
Today we will take a closer look at the nature of **ion channels** and how they are able to exhibit their remarkable properties that enable action potentials and all forms of electrical signaling in the nervous system.
Now we know from our previous classes covering the work by HH, that there are some predictions we make concerning the nature of ion channels:
Now we know from our previous classes covering the work by Hodgkin-Huxley, that there are some predictions we make concerning the nature of ion channels..
--
@@ -31,21 +31,6 @@ During the rising phase of the action potential:
Note:
So a quick question
Answer to myelinated question from last time:
[Hartline and Colman Curr Biol, 2007](http://www.sciencedirect.com/science/article/pii/S0960982206025231)
>It seems to have arisen independently in evolution several times in vertebrates, annelids and crustacea.
>absent in primitive members of the vertebrate line (hagfish and lampreys)
>Myelin has not been reported in either molluscs or insects
>The first myelinated vertebrate was likely to have been a placoderm [9], the antecedent of contemporary sharks and bony fish.
---
@@ -73,22 +58,25 @@ Can measure ion flow through a single channel.
Note:
---
--
## The patch clamp method
<div style="height:300px"><figcaption>Neuroscience 5e Box 4A</figcaption><img src="figs/Neuroscience5e-Box-04A-2R_58077da.jpg" height="200px"><figcaption class="big">
Can measure potentials and currents
from entire cell and introduce
things into the cytoplasm
</figcaption></div>
<div style="margin:0 25px; height:300px"><figcaption>Neuroscience 5e Box 4A</figcaption><img src="figs/Neuroscience5e-Box-04A-3R_8f113be.jpg" height="200px"><figcaption class="big">
Makes it easy to introduce things to
the cytoplasmic side of the channel
</figcaption></div>
<div><figcaption>Neuroscience 5e Box 4A</figcaption><img src="figs/Neuroscience5e-Box-04A-4R_1677b63.jpg" height="200px"><figcaption class="big">
<div style="margin:33px 0;"><figcaption>Neuroscience 5e Box 4A</figcaption><img src="figs/Neuroscience5e-Box-04A-4R_1677b63.jpg" height="200px"><figcaption class="big">
Makes it easy to introduce things to the extracellular side of the channel
</figcaption></div>
@@ -147,7 +135,8 @@ TEA
<div>
<div></div>
* Small inward currents
* Small (picoampere) inward currents
* Unitary amplitudes
* Open at beginning of pulse
* Inactivate quickly
@@ -158,12 +147,17 @@ TEA
Note:
Patch a piece of membrane and block K currents. Do a bunch of short recordings while clamping the membrane at depolarized potential. e.g. here is 7 trials. Notice the amplitude is discrete— it is unitary. If you were recording from lots of these single channels simultaneously or added together all the recordings from one channel you'd -->
Patch a piece of membrane and block K currents. Do a bunch of short recordings while clamping the membrane at depolarized potential. e.g. here is 7 experimental trials. **Notice the amplitude is discrete**— it is unitary. If you were recording from lots of these single channels simultaneously or added together all the recordings from one channel you'd -->
Transient channel opening in Na⁺ channels (inward current).
This research is from Bezanilla and Correa 1995, Vandenburg and Bezanilla 1991, Correa and Bezanilla 1994
unitary (wn, adj)
: one, unitary -- (having the indivisible character of a unit; "a unitary action"; "spoke with one voice")
---
## Measurements of ionic currents flowing through single Na⁺ channels
@@ -182,13 +176,12 @@ This research is from Bezanilla and Correa 1995, Vandenburg and Bezanilla 1991,
Note:
get something similar to this microscopic current shown at the top.
Average the microscopic currents together and you get something very similar.
Average the microscopic currents together and you get something very similar to this macroscopic voltage-clamp current shown at the top.
Sum these microscopic inwa
Notice that even at -20 to -10mV when you expect an action potential to be well into its rising phase above threshold, the probability of sodium channel opening is just 40-50% (and never reaches 100%).
This research is from Bezanilla and Correa 1995, Vandenburg and Bezanilla 1991, Correa and Bezanilla 1994
Bezanilla and Correa 1995, Vandenburg and Bezanilla 1991, Correa and Bezanilla 1994
---
@@ -268,7 +261,6 @@ Remember this figure from last time, shown here is a model of the functional sta
Note:
So the conclusions are…
---
@@ -375,13 +367,19 @@ from [channelpedia](http://channelpedia.epfl.ch/ionchannels/9):
>a voltage-activated A-type potassium ion channel and is prominent in the repolarization phase of the action potential. This gene is expressed at moderate levels in all tissues analyzed, with lower levels in skeletal muscle.
HERG channels inactivate so rapidly that current flows only when inactivation is rapidly removed at end of a depolarization
- inward rectifier K channels allow more K current to flow at hyperpolarized potentials than at depolarized potentials
* human Ether-à-go-go-Related Gene), best known for its contribution to the electrical activity of the heart that coordinates the heart's beating, mediates the repolarizing IKr current in the cardiac action potential).
* HERG channels inactivate so rapidly that current flows only when inactivation is rapidly removed at end of a depolarization
inward rectifier K channels allow more K current to flow at hyperpolarized potentials than at depolarized potentials
Ca activated K channels open in response to intracellular Ca ions
2-P K channels usually respond to chemical signals rather than changes in membrane potential. These are primarily responsible for the resting membrane potential of neurons. e.g. TASK channels can by regulated by extracellular pH
2-P K channels ("two-pore", or KCNK gene family, 50+ genes?) can respond to other signals (e.g. pH changes for the TASK (KCNK3 and KCNK9) channel subtypes) rather than changes in membrane potential and are important in regulating the ongoing membrate potential of neurons at "rest", playing a role in the historically termed "K<sub>leak</sub>" current.
<https://www.nature.com/articles/35058574>
<!-- ## Diverse properties of K⁺ channels
@@ -398,7 +396,6 @@ inward rectifier K channels allow more K current to flow at hyperpolarized poten
Ca activated K channels open in response to intracellular Ca ions
2-P K channels usually respond to chemical signals rather than changes in membrane potential. These are primarily responsible for the resting membrane potential of neurons. e.g. TASK channels can by regulated by extracellular pH
-->
@@ -518,7 +515,9 @@ K | 0.27 | 0.46
</div>
<div><img src="figs/K-channel-selectivity-filter_cf5a63c.jpg" width="300px"><figcaption>JA, [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></div>
<div><img src="figs/K-channel-selectivity-filter_cf5a63c.jpg" width="300px"><figcaption>
JA, [CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></div>
Note:
@@ -617,21 +616,8 @@ Yellow are voltage sensing tm domains
4–8 positively-charged amino acids in the S4 domain. Experiences force in a transmembrane electric field. Is the electric-field sensor for voltage-dependent gating.
K channels are more diverse
K channels are diverse
- Kv2.1 show little inactivation and are closely related to the delayed rectifier K channels involved in AP repolarization
- Kv4.1 channels inactivate during a depolarization.
HERG channels inactivate so rapidly that current flows only when inactivation is rapidly removed at end of a depolarization
* human Ether-à-go-go-Related Gene), best known for its contribution to the electrical activity of the heart that coordinates the heart's beating, mediates the repolarizing IKr current in the cardiac action potential).
inward rectifier K channels allow more K current to flow at hyperpolarized potentials than at depolarized potentials
Ca activated K channels open in response to intracellular Ca ions
2-P K channels usually respond to chemical signals rather than changes in membrane potential. These are primarily responsible for the resting membrane potential of neurons. e.g. TASK channels can by regulated by extracellular pH
<!-- Channel selectivity