thru fall2018 lecture04
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ackman678
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## Voltage dependent membrane permeability
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<div style="font-size:0.8em;">
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<div style="font-size:0.7em;">
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<div></div>
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* Hodgkin and Huxley hypothesis– Action potential can be explained by **voltage-gated ion channels**
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* Experiment– Measure ion permeability at varying membrane potentials
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* Problem– Difficult to systematically vary the cell potential and also measure ion permeability
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* Solution– Voltage clamping. Fix membrane potential in a cell without triggering an action potential while measuring ion permeability
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* Solution– Voltage clamping. Fix membrane potential in a cell without triggering an action potential while measuring ion permeability (~conductance)
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</div>
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@@ -16,19 +16,17 @@ Note:
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We learned last time that the experiments of Hodgkin, Huxley, and Katz showed that the Vm during an AP approaches ENa. And they thought that this might be due to changes in permeability for Na in the cell membrane that changes during the course of an action potential. Thus Hodgkin and Huxley hypothesized that APs can be explained by ion channels that change their permeability due to voltage— that these channels are voltage-gated.
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Alan Hodgkin and Andrew Huxley began this work in the late 1930s, and quickly finished one paper before helping with the British war effort during WWII. Indeed Hodgkin said that he lost all interest in neurophysiology during those dark years as one might imagine. But as things calmed down after the war they renewed their collaboration and got back to the business of neuronal excitability.
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Alan Hodgkin and Andrew Huxley began this work in the late 1930s, and quickly finished one paper before helping with the British war effort during WWII. Indeed Hodgkin said that he lost all interest in neurophysiology during those dark years as one might imagine. But as things calmed down after the war they renewed their collaboration and got back to the business of neuronal excitability.
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So they needed to proved that ion permeability changes according to membrane potential but there was an issue— how to vary the membrane potential in a systematic way and also measure the ion permeabilities?
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So they needed to proved that ion permeability changes according to membrane potential but there was an issue— how to vary the membrane potential in a systematic way and also measure the ion permeabilities?
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The solution was to build an electrophysiological recording apparatus with feedback circuitry such that you can fix or clamp the voltage across the cell membrane.
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[http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-7793/homepage/celebrating_the_work_of_alan_hodgkin_and_andrew_huxley.htm](http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-7793/homepage/celebrating_the_work_of_alan_hodgkin_and_andrew_huxley.htm)
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--
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---
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## Action potential summary video
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<div><video height=400px controls src="figs/Animation02-03TheActionPotential.mp4"></video><figcaption>Neuroscience 5e Animation 2.3</figcaption></div>
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<div><video height=400px controls src="figs/Animation02-03TheActionPotential.mp4"></video><figcaption>Neuroscience 5e Animation 2.3</figcaption></div>
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Note:
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@@ -36,7 +34,7 @@ Summary of last time…
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--
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## More Vm examples
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## More V<sub>m</sub> examples
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<div style="font-size:0.7em;">
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<div></div>
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@@ -52,39 +50,38 @@ Summary of last time…
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* <span class= "fragment fade-in">`Pk = 0.5; Pna = 0.5; Pcl = 0; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 11; clOut = 11`</span>
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* <span class= "fragment fade-in">`(58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) ) = 0 mV`</span>
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</div>
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</div>
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Note:
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1. (58/1)*log10(1/10) = -58 mV
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2. (58/1)*log10(10/1) = +58 mV
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3. (58/-1)*log10(11/11) = 0 mV
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1. `(58/1)*log10(1/10) = -58 mV`
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2. `(58/1)*log10(10/1) = +58 mV`
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3. `(58/-1)*log10(11/11) = 0 mV`
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4. 0 mV:
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* Pk = 0.5; Pna = 0.5; Pcl = 0; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 11; clOut = 11
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* (58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) ) = 0 mV
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* `Pk = 0.5; Pna = 0.5; Pcl = 0; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 11; clOut = 11`
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* `(58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) ) = 0 mV`
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* 0 mV:
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* Pk = 1; Pna = 1; Pcl = 0; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 11; clOut = 11
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* (58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) )
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* `Pk = 1; Pna = 1; Pcl = 0; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 11; clOut = 11`
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* `(58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) )`
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* -59 mV (room temp and low Pna):
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* Pk = 1; Pna = 0.001; Pcl = 0.5; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 1; clOut = 11
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* (58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut)
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*
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* `Pk = 1; Pna = 0.001; Pcl = 0.5; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 1; clOut = 11`
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* `(58)*log10( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut)`
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-62 mV (body temp and low Pna):
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-62 mV (body temp and low Pna):
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* R = 8.3; F = 9.6e4; T = (273+37)
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* Pk = 1; Pna = 0.001; Pcl = 0.5; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 1; clOut = 11
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* ((R*T)/F)*log( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) )
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* `Pk = 1; Pna = 0.001; Pcl = 0.5; kOut = 1; kIn = 10; naOut = 10; naIn = 1; clIn = 1; clOut = 11`
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* `((R*T)/F)*log( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) )`
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-69 mV (body temp and low Pna and physiol concentrations):
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-69 mV (body temp and low Pna and physiol concentrations):
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* R = 8.3; F = 9.6e4; T = (273+37)
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* Pk = 1; Pna = 0.05; Pcl = 0.45; kOut = 5; kIn = 140; naOut = 145; naIn = 5; clIn = 5; clOut = 110
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* ((R*T)/F)*log( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) )
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* `R = 8.3; F = 9.6e4; T = (273+37)`
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* `Pk = 1; Pna = 0.05; Pcl = 0.45; kOut = 5; kIn = 140; naOut = 145; naIn = 5; clIn = 5; clOut = 110`
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* `((R*T)/F)*log( (Pk*kOut + Pna*naOut + Pcl*clIn) / (Pk*kIn + Pna*naIn + Pcl*clOut) )`
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Calculate the total concentration of all ions for these solutions. For every one NaCl that dissolves, two ions are produced (one Na⁺ and one Cl¯). Thus for 10 mmol/L NaCl outside there are (10 mmol/L)x(1 total Cl ions/NaCl) = 10mM. And for 1mM KCl outside there are (1 mmol/L)x(1 total Cl ions/KCl) = 1mM. Thus the total number of Cl⁻ ions per liter is 11mmol/L = 11mM
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@@ -92,9 +89,11 @@ Calculate the total concentration of all ions for these solutions. For every one
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---
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## The voltage clamp method
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## The voltage clamp technique
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<div><img src="figs/Neuroscience5e-Box-03A-0R_5d20ab3.png" height="400px"><figcaption>Neuroscience 5e Box 3A</figcaption></div>
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Voltage clamping provides a method for measuring electrical current and its direction of net flow across a cell membrane.
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<div><img src="figs/Neuroscience5e-Box-03A-0R_5d20ab3.png" height="400px"><figcaption>Neuroscience 5e/6e Box 3A</figcaption></div>
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Note:
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@@ -107,9 +106,9 @@ voltage clamp amplifier compares membrane potential to the desired command poten
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When Vm is different from the command potential the clamp amplifier injects current ion the axon through a second electrode. This feedback arrangement causes the membrane potential to become the same as the command potential.
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The current flowing back into the axon and thus across its membrane can be measured.
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The current flowing back into the axon and thus across its membrane can be measured.
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**This electronic feedback circuit holds the membrane pot at the desired level, even in the face of permeability changes that would normally alter the membrane potential. (such as those generated during the action potential). Most importantly, the device permits the simultaneous measure of the current needed to keep the cell at a given voltage. This current is exactly equal to the amount of current flowing across the neuronal membrane, allowing direct measurement of these membrane currents.
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**This electronic feedback circuit** holds the membrane potential at the desired level, even in the face of permeability changes that would normally alter the membrane potential. (such as those generated during the action potential). Most importantly, the device permits the simultaneous measure of the current needed to keep the cell at a given voltage. This current is exactly equal to the amount of current flowing across the neuronal membrane, allowing direct measurement of these membrane currents.
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>An amplifier, electronic amplifier or (informally) amp is an electronic device that can increase the power of a signal. It does this by taking energy from a power supply and controlling the output to match the input signal shape but with a larger amplitude.
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@@ -121,7 +120,7 @@ The current flowing back into the axon and thus across its membrane can be measu
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---
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## Hodgkin and Huxley 1952
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## A. Hodgkin and A. Huxley 1952
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* Do neuronal membranes have voltage-dependent permeability?
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* Which ions are changing their permeability?
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@@ -130,7 +129,7 @@ The current flowing back into the axon and thus across its membrane can be measu
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Note:
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Hodgkin and Huxley published a series of seminal papers in 1952 that summarized their investigations using this voltage clamp method to examine voltage dependent ion flux.
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Alan Hodgkin and Andrew Huxley from the Univ of Cambridge published a series of seminal papers in 1952 that summarized their investigations using this voltage clamp method to examine voltage dependent ion flux.
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They asked…
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@@ -141,15 +140,18 @@ So the experiment was to hold the membrane potential at different voltages and m
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## Electric current flow across a squid axon membrane during voltage clamp
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<div><figcaption class="big">negligible current (except for a capacitive transient)</figcaption><img src="figs/Neuroscience5e-Fig-03.01-1R_5455913.png" height="300px"><figcaption>Neuroscience 5e fig. 3.1</figcaption></div>
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<div><figcaption class="big">negligible current (except for a capacitive transient)</figcaption><img src="figs/Neuroscience5e-Fig-03.01-1R_5455913.png" height="300px"><figcaption>Neuroscience 5e/6e fig. 3.1; from Hodgkin et al., *J. Physiol.* 1952</figcaption></div>
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<div><figcaption class="big">inward and outward currents</figcaption><img src="figs/Neuroscience5e-Fig-03.01-2R_49ec352.png" height="300px"><figcaption>Neuroscience 5e/6e fig. 3.1; from Hodgkin et al., *J. Physiol.* 1952</figcaption></div>
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<div style="font-size:0.7em; margin:25px 0;">Inward current is always downward deflection from zero in these traditional voltage clamp plots. Outward current is an upward deflection. </div>
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<div><figcaption class="big">inward and outward currents</figcaption><img src="figs/Neuroscience5e-Fig-03.01-2R_49ec352.png" height="300px"><figcaption>Neuroscience 5e fig. 3.1</figcaption></div>
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Note:
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And so here are the results from this type of voltage clamp experiment.
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If you command that the cell membrane potential be hyperpolarized, you get very little or negligible current flowing across the membrane except for a very brief capacitive current that you always see in these voltage clamp experiments.
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If you command that the cell membrane potential be hyperpolarized, you get very little or negligible current flowing across the membrane except for a very brief capacitive current that you always see in these voltage clamp experiments.
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This is because the cell membrane essentially acts as a parallel RC circuit where a resistor and a capacitor are connected in parallel and to a constant current source. Ion channels are resistors, lipid bilayer with the extracellular and intracellular environments act as capacitor, storing charge in the form of ions accumulating near the surface of the membrane. When a switch is turned on in an RC circuit current flows from the battery to the capacitor until the capacitor is charged to a voltage that is same as the battery.
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@@ -161,32 +163,40 @@ However when Hodgkin and Huxley depolarized the membrane, a transient inward cur
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* When the voltage is constant, the current through the capacitative pathway is zero because the capacitor has acquired the charge Q (coulombs) according to the relationship Q=CV. C is capacitance (farads) Ic is capacitive current. Ic = C(dV/dt)
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* as long as V is changing with time, there will be a current flowing towards the capacitor.
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* if V is constant in time, there is no capacitive current.
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* product of resistance and capacitance has the unit of time and is called the time constant. Time constant defines how quickly capacitors charge or discharge over time.
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* product of resistance and capacitance has the unit of time and is called the time constant. Time constant defines how quickly capacitors charge or discharge over time.
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[http://nerve.bsd.uchicago.edu/med98c.htm](http://nerve.bsd.uchicago.edu/med98c.htm)
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---
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## Current produced by different membrane depolarizations during voltage clamp
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## Inward & outward currents produced at a series of clamped membrane voltages
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<figure><img src="figs/Neuroscience5e-Fig-03.02-0_5ee332f.png" height="400px"><figcaption>Neuroscience Fig. 3.2</figcaption></figure>
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<figure><figcaption class="big">Voltage clamp recordings from squid axon. Capacitive artifact removed for clarity.</figcaption><img src="figs/Neuroscience5e-Fig-03.02-0_5ee332f.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.2; from Hodgkin et al., *J. Physiol.* 1952</figcaption></figure>
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Note:
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This show several different voltage steps (with the brief capacitive current omitted for clarity)
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...Notice as we approach ENa the inward current disappears.
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Notice a few phenonmena in this figure.
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---
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...Notice as the command voltage becomes more positive we start to approach ENa and the inward current disappears.
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--
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## Relationship between current amplitude and membrane potential
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<figure><figcaption class="big">External Na⁺ 440 mM, internal Na⁺ 50 mM, therefore Nernst says **E<sub>Na</sub> = 55 mV**</figcaption><img src="figs/voltage_clamp_currents_summary_plot_7450e0a.png" height="400px"><figcaption>Neuroscience 5e Fig. 3.3</figcaption></figure>
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<figure><figcaption class="big">External Na⁺ 440 mM, internal Na⁺ 50 mM, therefore Nernst says **E<sub>Na</sub> = 55 mV**</figcaption><img src="figs/voltage_clamp_currents_summary_plot_7450e0a.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.3; from Hodgkin et al., *J. Physiol.* 1952</figcaption></figure>
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Note:
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This summarizes the peak magnitude of these these two currents at different Vm
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Don't get confused by this plot, look at the axes it is just Vm and current.
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Bascially this just summarizes the peak magnitude of these these two currents at different Vm in the previous figure 3.2.
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---
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@@ -197,13 +207,14 @@ This summarizes the peak magnitude of these these two currents at different Vm
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Note:
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So it seems like this inward current may be carried by Na ions.
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So it seems like this inward current may be carried by Na ions.
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---
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## Dependence of the early inward current on sodium
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<div><img src="figs/Neuroscience5e-Fig-03.04_0d877f5.png" height="500px"><figcaption>Neuroscience 5e Fig. 3.4</figcaption></div>
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<div><img src="figs/Neuroscience5e-Fig-03.04_0d877f5.png" height="500px"><figcaption>Neuroscience 5e/6e Fig. 3.4; from Hodgkin and Huxley *J. Physiol.* 1952a</figcaption></div>
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<div><iframe src="https://www.youtube.com/embed/Wd_gKJoo25Y" width="420" height="315"></iframe><figcaption>Squid giant axon voltage clamping</figcaption></div>
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@@ -218,7 +229,7 @@ Note:
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## Voltage clamp method summary
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<div><video height=400px controls src="figs/Animation03-01TheVoltageClampMethod.mp4"></video><figcaption>Neuroscience 5e Animation 3.1</figcaption></div>
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<div><video height=400px controls src="figs/Animation03-01TheVoltageClampMethod.mp4"></video><figcaption>Neuroscience 5e Animation 3.1</figcaption></div>
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Note:
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@@ -243,7 +254,7 @@ Note:
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* Fugu (puffer fish or blow fish)
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* TTX concentrated in their livers (don’t eat it)
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* TTX blocks voltage-gated Na⁺ channels
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* TTX blocks voltage-gated Na⁺ channels
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</div>
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@@ -258,12 +269,12 @@ Its mechanism of action, selective blocking of the sodium channel, was shown def
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## Pharmacological separation of inward and outward currents into Na⁺ and K⁺ dependent components
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<figure><img src="figs/Neuroscience5e-Fig-03.05-0_99fe22f.png" height="400px"><figcaption>Neuroscience 5e Fig. 3.5</figcaption></figure>
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<figure><img src="figs/Neuroscience5e-Fig-03.05-0_99fe22f.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.5; from Moore et al. *J Gen Physiol* 1967 and Armstrong and Binstock *J Gen Physiol* 1965</figcaption></figure>
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Note:
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Tetramethylammonium chloride is one of the simplest quaternary ammonium salts.
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Tetramethylammonium chloride is one of the simplest quaternary ammonium salts.
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[https://en.wikipedia.org/wiki/Tetramethylammonium_chloride](https://en.wikipedia.org/wiki/Tetramethylammonium_chloride)
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@@ -279,13 +290,13 @@ TTX and TEA experiments from Moore 1967 J Gen Physiol; Armstrong and Binstock, 1
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* Another way of describing permeability is using membrane conductance (*g*). Conductance (measured in siemens, *S*) is the reciprocal of resistance
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* *g = 1/R*
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* Ohm’s law:
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* Ohm’s law:
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* *I = V/R*
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* *I = gV*
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* For an ion *x*,
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* *I<sub>x</sub>* = ionic current flow, *E<sub>x</sub>* = equilibrium potential
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* The membrane potential (*V<sub>m</sub>*) minus the equilibrium potential (*E<sub>x</sub>*) is the electrochemical driving force acting on an ion, thus *V = V<sub>m</sub> - E<sub>x</sub>*
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* *I<sub>x</sub> = g<sub>x</sub>*
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* *I<sub>x</sub> = g<sub>x</sub>V*
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* *I<sub>x</sub> = g<sub>x</sub>(V<sub>m</sub> - E<sub>x</sub>)*
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* Solve for *g*:
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* *g<sub>x</sub> = I<sub>x</sub>/(V<sub>m</sub> - E<sub>x</sub>)*
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@@ -296,7 +307,7 @@ TTX and TEA experiments from Moore 1967 J Gen Physiol; Armstrong and Binstock, 1
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Note:
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For our purposes, we can consider conductance to be another way of describing permeability.
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For our purposes, we can consider conductance to be another way of describing permeability.
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technically conductance is the degree to which an object conducts electricity, calculated as the ratio of the current that flows to the potential difference present. It deals with the movement of charge, whereas permeability refers to the ability of a specific ion to move across the cell membrane.
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@@ -311,7 +322,7 @@ Can use this to calculate the dependence of Na and K conductances vs. time and m
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## Membrane conductance changes are time and voltage dependent
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<div><img src="figs/Neuroscience5e-Fig-03.06-0_757dbce.png" height="400px"><figcaption>Neuroscience Fig. 3.6</figcaption></div>
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<div><img src="figs/Neuroscience5e-Fig-03.06-0_757dbce.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.6; from Hodgkin and Huxley *J Physiol* 1952b</figcaption></div>
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Note:
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@@ -322,7 +333,7 @@ Note:
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## Depolarization increases Na⁺ and K⁺ conductances of the squid giant axon
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<div><img src="figs/Neuroscience5e-Fig-03.07-0_fdae974.png" height="400px"><figcaption>Neuroscience Fig. 3.7</figcaption></div>
|
||||
<div><img src="figs/Neuroscience5e-Fig-03.07-0_fdae974.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.7; from Hodgkin and Huxley *J Physiol* 1952b</figcaption></div>
|
||||
|
||||
|
||||
Note:
|
||||
@@ -336,8 +347,8 @@ Determine the peak conductance of ions at different membrane potentials.
|
||||
<div style="font-size:0.8em;">
|
||||
<div></div>
|
||||
|
||||
* At rest (-70 mV), voltage-gated Na⁺ and K⁺ channels are closed. Non voltage-gated K⁺ channels are open and dictate the resting potential, together with the distribution of ions across cell membranes
|
||||
* A stimulus raises the membrane potential in the cell. Depolarization causes voltage-gated Na⁺ channels to open, which allows Na⁺ to rush in the cell which increases the membrane potential, which causes more Na⁺ channels to open, which causes more Na⁺ to rush in which causes higher membrane potential (a positive feedback loop). As membrane potential is approaching E<sub>Na</sub>, the further depolarization causes Na⁺ channels to inactivate which prevents more Na⁺ from from flowing through these channels
|
||||
* At rest (-70 mV), voltage-gated Na⁺ and K⁺ channels are closed. Non voltage-gated K⁺ channels (K<sub>leak</sub>) are open and dictate the resting potential, together with the distribution of ions across cell membranes
|
||||
* A stimulus raises the membrane potential in the cell. Depolarization causes voltage-gated Na⁺ channels to open, which allows Na⁺ to rush in the cell which increases the membrane potential, which causes more Na⁺ channels to open, which causes more Na⁺ to rush in which causes higher membrane potential (a positive feedback loop). As membrane potential is approaching E<sub>Na</sub>, the further depolarization causes **Na⁺ channels to inactivate** which prevents more Na⁺ from from flowing through these channels
|
||||
* Depolarization also opens voltage gated K⁺ channels, which causes K⁺ to flow out, thus lowering the membrane potential
|
||||
|
||||
</div>
|
||||
@@ -349,11 +360,17 @@ Note:
|
||||
|
||||
## Ion conductances underlying the action potential
|
||||
|
||||
<figure><img src="figs/Neuroscience5e-Fig-03.08-1R_efbfb99.png" height="400px"><figcaption>Neuroscience 5e Fig. 3.8</figcaption></figure>
|
||||
<figure><img src="figs/Neuroscience5e-Fig-03.08-1R_efbfb99.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.8</figcaption></figure>
|
||||
|
||||
Note:
|
||||
|
||||
Summary of the conductances for Na and K during an action potential.
|
||||
|
||||
Based on Hodgkin and Huxley's mathematical model for the action potential (1952d).
|
||||
|
||||
Can see that the neuronal membrane becomes much less resistant to Na flux during the rising phase of the AP.
|
||||
|
||||
Can also see increases in K conductance during the AP, but this K+ conductance (underlying the outward current) are slow and sustained reaching peak permeability during the falling phase of the AP. Note when the cell is back to Vrest, the gK is still moderately high before ramping down. This is important for the refractory period.
|
||||
|
||||
<!-- ## Feedback cycles responsible for membrane potential changes
|
||||
|
||||
@@ -366,10 +383,10 @@ Note:
|
||||
<div style="font-size:0.8em;">
|
||||
<div></div>
|
||||
|
||||
* Question– Why do APs exhibit an all-or-nothing threshold?
|
||||
* Answer– When membrane potential (V<sub>m</sub>) is below threshold there is not enough Na⁺ channels open to raise V<sub>m</sub> high enough to open more channels. When V<sub>m</sub> is above threshold the 'explosive' action potential cycle is activated.
|
||||
* Question– Why to APs exhibit an undershoot?
|
||||
* Answer– During the AP voltage-gated K⁺ conductance slowly increases (delayed activation of voltage-gated K⁺ channels) and during the falling phase these K⁺ channels are still open and active whereas voltage-gated Na⁺ channels are inactivated… as V<sub>m</sub> approaches E<sub>k</sub> there is briefly more K⁺ flowing out than at rest and the hyperpolarization inactivates voltage-gated K⁺ channels. K⁺ leak channels and ion transporters bring back cell to resting potential.
|
||||
* Question– Why do APs exhibit an all-or-nothing threshold?
|
||||
* <span>Answer– When membrane potential (V<sub>m</sub>) is below threshold there is not enough Na⁺ channels open to raise V<sub>m</sub> high enough to open more channels. When V<sub>m</sub> is above threshold the 'explosive' action potential cycle is activated.</span> <!-- .element: class="fragment fade-in"-->
|
||||
* Question– Why to APs exhibit an undershoot? <!-- .element: class="fragment fade-in"-->
|
||||
* <span>Answer– During the AP voltage-gated K⁺ conductance slowly increases (delayed activation of voltage-gated K⁺ channels) and during the falling phase these K⁺ channels are still open and active whereas voltage-gated Na⁺ channels are inactivated… as V<sub>m</sub> approaches E<sub>k</sub> there is briefly more K⁺ flowing out than at rest and the hyperpolarization inactivates voltage-gated K⁺ channels. K⁺ leak channels and ion transporters bring back cell to resting potential.</span> <!-- .element: class="fragment fade-in"-->
|
||||
|
||||
</div>
|
||||
|
||||
@@ -407,7 +424,7 @@ During an action potential, inward current through Na⁺ channels
|
||||
|
||||
## Passive current flow in an axon
|
||||
|
||||
<figure><figcaption class="big">subthreshold changes diffuse rapidly</figcaption><img src="figs/Neuroscience5e-Fig-02.03-1R_aac41b9.png" height="400px"><figcaption>Neuroscience 5e Fig. 2.3</figcaption></figure>
|
||||
<figure><figcaption class="big">subthreshold changes decay rapidly</figcaption><img src="figs/Neuroscience5e-Fig-02.03-1R_aac41b9.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 2.3</figcaption></figure>
|
||||
|
||||
|
||||
Note:
|
||||
@@ -418,13 +435,13 @@ bottom graph shows the peak Vm
|
||||
|
||||
## Propagation of an action potential
|
||||
|
||||
<figure><figcaption class="big">suprathreshold depolarizations propagate down the axon</figcaption><img src="figs/Neuroscience5e-Fig-02.03-2R_4bea3b6.png" height="400px"><figcaption>Neuroscience 5e Fig. 2.3</figcaption></figure>
|
||||
<figure><figcaption class="big">suprathreshold depolarizations propagate down the axon and don't decay</figcaption><img src="figs/Neuroscience5e-Fig-02.03-2R_4bea3b6.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 2.3</figcaption></figure>
|
||||
|
||||
Note:
|
||||
|
||||
bottom graph shows the peak Vm
|
||||
|
||||
<!--
|
||||
<!--
|
||||
|
||||
## Action potential conduction requires both active and passive current flow
|
||||
|
||||
@@ -454,7 +471,7 @@ Active and Passive current flow.
|
||||
<div style="font-size:0.8em;">
|
||||
<div></div>
|
||||
|
||||
* Remember during the falling to undershoot phase of an action potential K⁺ channels are still open but Na⁺ are channels inactivated (decreased g<sub>Na</sub>), leading to temporary hyperpolarization more negative than the resting membrane potential
|
||||
* Remember during the falling to undershoot phase of an action potential K⁺ channels are still open but Na⁺ are channels inactivated (decreased g<sub>Na</sub>), leading to temporary hyperpolarization more negative than the resting membrane potential
|
||||
* Therefore (1) inactivation of Na⁺ channels and (2) slow K⁺ channel kinetics are responsible for the refractory period
|
||||
* This makes it harder to initiate a new AP either from a new stimulus or for an AP to propagate backwards
|
||||
* Different axons will have different refractory periods (and thus different maximal firing rates) depending on the particular subtypes of Na⁺ and K⁺ channels they express
|
||||
@@ -505,7 +522,7 @@ Note:
|
||||
|
||||
saltatory action potential condution along a myelinated axon
|
||||
|
||||
<!--
|
||||
<!--
|
||||
|
||||
## Nodes of Ranvier
|
||||
|
||||
@@ -539,13 +556,13 @@ action potential genaration occurs only at specific points, the nodes of Ranvier
|
||||
|
||||
<div style="width:300px; float:left;"><img src="figs/q002_155484b.jpg" height="200px"><figcaption class="big">
|
||||
|
||||
Alan Lloyd Hodgkin
|
||||
Alan Lloyd Hodgkin
|
||||
|
||||
</figcaption></div>
|
||||
|
||||
<div style="width:600px; float:left;"><img src="figs/q003hux_505f8c6.jpg" height="200px"><figcaption class="big">
|
||||
|
||||
Andrew Fielding Huxley
|
||||
Andrew Fielding Huxley
|
||||
|
||||
</figcaption></div>
|
||||
|
||||
@@ -587,7 +604,7 @@ onset between ages 20-40.
|
||||
|
||||
blindness, motor weakness, paralysis.
|
||||
|
||||
ultimate cause of MS remains unclear. Immune system contributes to damage and is key component. Immune cells in CSF and injection of myelin in animals can cause EAE. Autoimmune disorder. Or persistent infection with a human retrovirus?
|
||||
ultimate cause of MS remains unclear. Immune system contributes to damage and is key component. Immune cells in CSF and injection of myelin in animals can cause EAE. Autoimmune disorder. Or persistent infection with a human retrovirus?
|
||||
|
||||
|
||||
* women to men ratio 3/2
|
||||
|
||||
Reference in New Issue
Block a user