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neurophysiology1.md
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# Neuronal signaling
* Electrical signals of nerve cells
* Electrical signals of nerve cells <!-- .element: class="fragment highlight-green" -->
* Voltage-dependent membrane permeability
* Channels and transporters
* Synaptic transmission
* Neurotransmitters, receptors, and their effects
* Molecular signaling within neurons
* Neurotransmitters, receptors, and their effects (second messenger systems, molecular signaling within neurons)
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Note:
@@ -14,9 +15,7 @@ So, how do neurons convey information over long distances that results in inform
- voltage-dependent membrane permeability
- which in turn requires special membrane proteins called ion channels and transporters
- synaptic transmission
- which in turn requires neurotransmitters, their membrane bound protein receptors and their resulting effects
as well as general molecular signaling within neurons as any living cell might have
- which in turn requires neurotransmitters, their membrane bound protein receptors and their resulting effects, including general molecular signaling within neurons as any living cell might have
@@ -33,11 +32,11 @@ as well as general molecular signaling within neurons as any living cell might h
</div>
<div style="margin:0 15px;"><img src="figs/neuron_model-oscilloscope_a84cec9.png" width="300px"><figcaption></figcaption></div>
<div style="margin:0 15px;"><img src="figs/neuron_model-oscilloscope_a84cec9.png" width="300px"><figcaption>JA, CCO</figcaption></div>
Note:
To understand the basis of electrical excitability in neurons, we first need to understand that neurons, like other excitable cells, have a difference in electrical potential across the cell membrane when it is at rest.
To understand the basis of electrical excitability in neurons, we first need to understand that neurons, like other living cells, have a difference in electrical potential across the cell membrane when it is at rest.
To learn this physiologists stick electrodes inside of cells, including neurons. This electrode is hooked up to a voltmeter and another electrode sits outside the cell as a ground or reference electrode to complete the circuit. The difference in voltage between the inside of the cell and the outside of the cell is monitored over time and displayed on an oscilloscope.
@@ -107,7 +106,7 @@ mole
electricity
: movement of charged carriers through a medium in presence of electric field
: duality of electromagnetic waves as wave or particle
: AC (oscillation of electrons in place) vs DC (movment of electrons)
: AC (oscillation of electrons in place) vs DC (movement of electrons)
100 m/s == 360K m/hr == 223 mph
@@ -117,8 +116,8 @@ electricity
* Can be generated by changing the membrane potential of the neuron
* Receptor potentials can be generated from the activation of sensory receptors, from touch, light, sound, and heat
* Synaptic potentials are transmitted from one neuron to another at the synapse
* Action potentials are the booster system to propagate electrical signals a long distance
* Synaptic potentials are generated at the post-synaptic membrane between two neurons
* Action potentials are the high-amplitude, fast timing, regenerative signal that propagate a long distance
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@@ -151,7 +150,7 @@ To understand the basis of these electrical signals we first need to learn about
---
## Resting membrane potential of neurons
## What is baseline? The resting membrane potential of neurons
<div style="font-size:0.9em;">
<div></div>
@@ -163,7 +162,7 @@ To understand the basis of these electrical signals we first need to learn about
</div>
<div><img src="figs/lipid_bilayer_519d59a.png" height="200px"><figcaption></figcaption></div>
<div><img src="figs/lipid_bilayer_519d59a.png" height="200px"><figcaption>JA, CC0</figcaption></div>
@@ -175,12 +174,12 @@ We can think of the cell, a bit like American politics, is polarized with one si
This polarization of the cell results in a potential difference across the membrane (remember our water pump example) of about -70 mV
And its there is a concentration gradient in ions (which are charged atoms like sodium, potassium, and chloride) that results in this difference in distribution of charge across the neuron’s membrane
And there is a concentration gradient in ions (which are charged atoms like sodium, potassium, and chloride) that results in this difference in distribution of charge across the neuron’s membrane
---
## Important terms
## Cell membrane potential difference terms
* Resting membrane potential– voltage across the cell membrane when it is at rest. Typically –40 to –90 mV
* Hyperpolarization– making the membrane potential more negative
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Some important terms to know
Just remember that a neuron not eliciting any electrical signals is ‘resting’ at around -70 mV. If electrical current makes the membrane voltage more positive than it is depolarizing. If it is making the membrane more negative than it is hyperpolarizing. Depolarized is less polarized. Hyperpolarized is less polarized.
A neuron not eliciting any electrical signals is "resting" at around -70 mV. If electrical current makes the membrane voltage more positive than it is depolarizing. If it is making the membrane more negative than it is hyperpolarizing. Depolarized is less polarized. Hyperpolarized is more polarized.
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@@ -678,7 +677,7 @@ For a typical neuron at rest, pK : pNa : pCl = 1 : 0.05 : 0.45. Note that becaus
---
## Cells are like this container
## Cells are semi-permeable containers
* Semi permeable membranes
* Concentration gradients of ions across membranes
@@ -690,7 +689,9 @@ For a typical neuron at rest, pK : pNa : pCl = 1 : 0.05 : 0.45. Note that becaus
Note:
Cells are a bit like a semipermeable bag of electrolytes with different concentrations of ionic species inside and outside.
Cells are like a semipermeable bag of electrolytes with different concentrations of ionic species inside and outside.
That is semipermeable containers with some capactity for self-replication
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Table of physiological relevant intracellular and extracellular ion concentrations in squid neurons and mammalian neurons. Though the values are scaled about 4 times higher in squid, note that K is more concentrated inside, and sodium and chloride are more concentrated outside for both invertebrate and vertebrate neurons. The relevant ratios of different ion species inside and outside are similar.
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## How to test if a neuron is only permeable to K⁺ at rest
## Which ion fluxes are responsible for baseline- the resting potential?
* Need to measure concentrations of ions extracellularly and in the cytoplasm
* Would like to manipulate concentrations of ions outside as well as inside the cell
* Be able to make reliable electrical measurements
* Need an axon big enough to get your electrode in. Initially used the squid giant axon for experiments because they are large (400x larger than a typical mammalian axon).
How to test if a neuron is only permeable to K⁺ at rest?
* Measure concentrations of ions extracellularly and in the cytoplasm
* Manipulate concentrations of ions outside as well as inside the cell
* Make electrical measurements
* Choose a suitable physiological model
* Need an axon big enough to get your electrode in.
* Use squid giant axon for experiments. large, unmyelinated axons (400x larger than a typical mammalian axon)
Note:
How do we know the relative permeability of the neuronal membrane at rest or during action potentials?
As I hinted at earlier today and in a previous lecture, the squid giant axon was used to test the basic properties of electrical conduction in neurons in the 1930s to 1950s due to its mm sized diameter.
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## Squid giant axon
<div><img src="figs/Squid_Loligo_pealei_cbafe46.jpg" height="300px"><figcaption>Atlantic squid, *Loligo pealei*</figcaption></div>
<div><iframe src="https://www.youtube.com/embed/I6jxrxcLxiI" width="560" height="315"></iframe><figcaption>Squid giant axon electrophysiology</figcaption></div>
Note:
Need a physiological model suitable for the available experimental techniques.
The squid giant axon was used to test the basic properties of electrical conduction in neurons in the 1930s to 1950s due to its mm sized diameter.
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Alan Hodgkin, Andrew Huxley, Bernard Katz
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## Squid giant axon
<div><img src="figs/Squid_Loligo_pealei_cbafe46.jpg" height="300px"><figcaption>Atlantic squid, *Loligo pealei*</figcaption></div>
<div><iframe src="https://www.youtube.com/embed/I6jxrxcLxiI" width="560" height="315"></iframe><figcaption>Squid giant axon electrophysiology</figcaption></div>
Note:
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@@ -873,14 +879,14 @@ So a summary of the Hodgkin and Katz experiment conclusions...
## Resting membrane and action potentials entail permeabilities to different ions
## Resting membrane and action potentials comprise differing relative permeabilities to different ions
<figure><img src="figs/Neuroscience5e-Fig-02.07-0_caebcb8.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 2.7</figcaption></figure>
Note:
And as we will soon lecarn, the resting membrane potential and action potential voltage is mostly due to changes in K permeability and Na permeability across the neuronal membrane. As you can see in this figure, the resting membrane potential for a neuron is close to the EK eq potential due to much greater permeability for K. During an action potential Na permeability initially increases, until the Vm approaches the ENa and then Na permeability decreases until the Vm again approaches the resting membrane potential and Pk increases.
And as we will soon learn, the resting membrane potential and action potential voltage is mostly due to relative changes in the permeability of the membrane to and Na vs K across the neuronal membrane. As you can see in this figure, the resting membrane potential for a neuron is close to the EK eq potential due to much greater permeability for K. During an action potential Na permeability initially increases, until the Vm approaches the ENa and then Na permeability decreases until the Vm again approaches the resting membrane potential and Pk increases.
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