NEU 490 Membrane Potential Flashcards

1
Q

What drives ion movement across a permeable membrane? - ion movement affects neuron at rest + sending and receiving info from other neurons

Electrochemical gradient:?

A

Concentration - chemical driving force
Move down chemical gradient from high to low concentration
Can either have drive to leave (higher concentration inside than outside) or drive to enter (higher concentration outside than inside)

Electrical charge differences across membrane
Opposite charges attract (+ attracted to -)
Same charges repel (+ repel by +)
Positive driven to enter bc of the negative charges within the interior of the cell
Negatively charged ion that is driven to leave cell bc it is repelled away from negative chargers and attracted by the positive chargers on the outside of the cell

Ion flow is driven by the push and pull of the concentration of chemical gradients and electrical gradients

Electrochemical gradient: summation of the two individual gradients and providing a single direct of ion movement

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2
Q

Membrane Potential:?

Electrical Gradient (ions charged):?

Chemical Gradient:?

In non charged and nonpolar items like glucose only need to consider?

A

Membrane Potential: Determined by the difference between the electrical gradient (difference in electrical charge across the membrane) and the chemical gradient (concentration of ions across the membrane). Measured in millivolts (mV).

Electrical Gradient (ions charged): Opposes the chemical gradient. Represents the difference in electrical charge across the membrane (electrical potential difference = voltage)

Chemical Gradient (ions have chemical gradient bc different concentration in extracellular and intracellular compartments): Opposes the electrical gradient Represents the difference in the concentration of a specific ion across the membrane. (chemical potential difference - typically measured in mM)

In non charged and nonpolar items like glucose only need to consider chemical gradient because any differences in charges across the membrane have no effect on the movement of an nonpolar molecule. Only concentration difference is driving any movement.

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3
Q

Electrochemical Equilibrium (single ion):

At equilibrium

A

Chemical and electrical driving forces are equal in magnitude

Membrane potential (Vm) that is established at equilibrium is said to be the equilibrium potential (Veq.= Ex) for that ion under the existing concentration gradient

No net flux of ion - ions can still move through open channels but there’s no NET movement (meaning can have one ion move from inside to outside but another ion is moving outside to inside so they are canceling each other out)

[Ex = equilibrium potential for single ion (x) calculated via Nernst Equation] - for an individual ion crossing the membrane

Membrane potential established at this equilibrium of no net flux is said to be the equilibrium potential is known as Ex and that is the equilibrium potential for that ion

At equilibrium
No energy needed to maintain membrane voltage
Initial ion gradient is (almost) unchanged

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4
Q

Why high intracellular potassium?

why Na high out?

A

Why high intracellular potassium? It is apparently linked to all nucleotide-based life (animal, plant, bacteria) and important for protein synthesis. - this happening inside the cell so K is important for a lot of intracellular work

The sodium pump appears to be tied to osmotic and cell volume control/drive - maintains concentration gradient and resting membrane potential back after AP.

Ion Potassium - intracellular 140-150, extracellular 4-5 - highest number of leak channels

Ion Sodium - intracellular 5-15, extracellular 145 - low amount of leak channels

Ion Chloride - intracellular 4-30, extracellular 110 - next highest number of leak channels (not much impact bc equilibrium potential of chloride sits close to the resting membrane potential)

Ion Calcium - intracellular 0.0001, extracellular 1-2 - don’t have Ca leak channels really

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5
Q

Electrochemical Equilibrium -resting membrane potential (multiple ions to cross):

A

Chemical and electrical driving forces are equal in magnitude

Membrane potential that is established at equilibrium is said to be the equilibrium potential (Veq.) for those ions under the existing concentration gradient - permeability of the membrane to those ions

No net flux of ion: [Veq = membrane potential calculated via GHK Equation]

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6
Q

Resting Membrane Potential (RMP)

Difference in?

RMP is maintained by: what four

A

Difference in electrical potential (difference in net electrical charge) on either side of the membrane, measured in volts (mV). Reference electrode in extracellular and recording electrode in cell body of neuron intracellular

  1. Asymmetric distribution of ions across the plasma membrane (i.e., ion concentration gradients)
  2. Selective ion channels in the plasma membrane (K+ leak channels - present in greatest amounts) permeability to different ions
  3. Impermeable Anions - that are stuck inside cell and can not cross
  4. Na+/K+ ATPase - maintain concentration gradients

Concentration of different ions lead to varying degrees of electrochemical gradients in different directions like drive Na in and K out
Inside more negative and changer compare to the outside

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7
Q

A membrane at Rest - ions are distributed unequally — 3 things

Na/K ATPase?

The greater the ion’s concentration and permeability, the ?

A
  1. K diffuses down their steep concentration gradient (out of the cell) via leakage channels. Loss of K results in a negative charge on the inner plasma membrane face.
  2. K also move into the cell because they are attracted to the negative change established on the inner plasma membrane face.
  3. A negative membrane potential (-90) is established when the movement of K out the cell equals K movement into the cell. At this point the concentration gradient promoting K exists exactly opposes the electrical gradient for K entry.
    EK = -84→ -90
    RMP = -70 close to EK for K and Na helps make more positive

More permeable to K(highly permeable to k and inside has high concentration of k and low concentration on extracellular), due high intracellular with low extracellular concentration have a movement from inside to outside cell so move down concentration gradient and the positive ions moving cause the anions native on membrane lineup and the pull back some K back into cell

Na/K ATPase - essential for maintaining the concentration gradients of our ions - pumps 3 Na out and 2 K in

A small number of sodium ions continually leak into the cell. This makes the membrane potential more positive, weakening the electrical restraint on the movement of K ions. A small number of ions now leak out of the cell.

As Na ions accumulate in the cytosol, they are pumped outward in the exchange for K ions by the Na/K pump. The result is a low concentration of Na ions inside the cell. Some Na ions in the cytosol cause the membrane potential to be more positive than the equilibrium membrane potential for K.

The greater the ion’s concentration and permeability, the more it contributes to the resting membrane potential

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8
Q

Flux:

Influx:

Efflux:

Voltage:

Current:

Resistor:

Capacitor:

Battery:

A

Flux: the movement of charges

Influx: the net movement of ions into the cell from the extracellular fluid (ECF).

Efflux: the net movement of ions out of the cell to the ECF.

Voltage: the electric potential between two points

Current: the flow of electric charge, which is both the movement of electrons and ions in solution

Resistor: an electrical component that limits or regulates the flow of electrical current in an electronic circuit

Capacitor: devices where equal and opposite charges are held on separate “plates”, with a potential difference between them proportional to this charge - further way plates the lower capacitance and larger plates are the larger capacitance

Battery: a device that stores chemical energy, and converts it to electricity

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9
Q

Illustration of sodium’s electrochemical potential

A

At rest, both the concentration and electrical gradients for sodium point into the cell. As a result, sodium flows in. - chemical gradient is chargers from with side is from concentration gradient on either side of permeable membrane
As sodium enters, the membrane potential of the cell decreases and becomes more positive. Na higher on ECF and low on ICF chemical gradient is then pushing in. When get to 0 still have concentration wanting to enter but electrical is opposite so interior is positively charged
As the membrane potential changes, the electrical gradient decreases in strength, and after the membrane potential passes 0 mV, the electrical gradient will point outward, since the inside of the cell is more positively charged than the outside.
The ions will continue to flow into the cell until equilibrium is reached. At equilibrium have equal drive for both gradients.
If go above positive 60 the direction of Na would flow out of the cell bc too positive for electrical gradient is larger than concentration or chemical gradient so push put the Na ions. Above equilibrium potential or below for potassium the electrical gradient will be the driving force. Until reaching that point for K or Na concentration gradient is the driver.

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10
Q

Neuronal Membranes acts as Electrical Circuits (RC)

A

The neuronal membrane can be modeled by something called an RC circuit, where capacitance and resistance are in parallel. - ion channel resistor and membrane capacitor

Membrane resistance decrease with the number of open ion channels - the opening and closing of ion channel ligand or VG can affect resistance of membrane or with leak channels how much is covered can effect retsince

In the neuronal membrane, ion channels act as variable resistors

The membrane of a neuron is often related to a capacitor because of its ability to store and separate a charge on either side of a nonconducting material (ie. The lipid bilayer)

The concentration gradient of a neuron is the external to internal ratio of ion concentration, and can be represented with a battery in this RC circuit.

Neuron ion at rest have more than one particular ion channel bc permeable to more than ion so when look at rest open channels are different than AP - open leak channels and concentrations gradient for each gives battery

This is only showing leak channels, and during an action potential this circuit changes

The G for each ion channel is the conductance through the channel, and can be considered similar to the permeability of the membrane to that particular leak channel

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11
Q

Axons as Cables - all or none principle

Cable theory?

Axons are modeled as cylinders that are composed of segments with

A

Let’s think about how we are able to have action potentials travel down an axon and not weaken or decay along the length of the axon . Their morphology affects their function, and we can understand how they send signals by studying their cable properties.

The physics of charges moving down the length of axons is similar to the development of transatlantic cables in the 1800s.
Cable theory was developed in the mid-nineteenth century, by Lord Kelvin and others, in response to the need to lay long transatlantic cables that were able to send signals across long distances without having decay

Axons are modeled as cylinders that are composed of segments with capacitances (Cm) and resistances (Rm), combined in parallel. The resistance in series along the fiber (Ri) is due to the internal resistance of the axon (also sometimes shown as Ra for axoplasm resistance).
- Membrane resistance number of ion open channels
- Internal resistance or axoplasm resistance - affected by diameter of axon and have parallel RC circuits and then have internal resistance and can calculate how voltage will move through the circuit when change the conductance so VG ion channels below threshold have zero conductance which is G which is 1/G so conductance and resistance go hand in hand

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12
Q

Transatlantic cables required boosters in order to avoid decay of the signal across long distances.
What do you think is equivalent to the booster in an axon?

A

Nodes of ranvier in myelinated axons have VG Na channels so in myelinated axons at Nodes but in unmyelinated it VG Na channels so must have them spaced out. Dendrites don’t have Na all the way down so they decay
VG Na sodium channels - booster and amplifier

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13
Q

voltage-clamp electrophysiology?

Voltage clamp studies?

A

Voltage-dependent Membrane Permeability - How readily ions move through their channels based and how AP initiated on membrane permeability can be plotted using voltage-clamp electrophysiology. This is dependent on voltage.
We can calculate these charges moving across the membrane, which are referred to as ionic currents.

It is the sum of the various currents flowing at any point in time that determines the neuron’s membrane potential.
Thus the normal firing pattern of a neuron, and its response to different kinds of stimulation, can be seen as a play of interactions among the currents flowing through the different kinds of ion channels in its membrane.
The activities of the sodium and potassium channels responsible for axonal action potentials are themselves dependent on voltage.

Voltage clamp studies: which allow the measurement of the current flowing through these channels at fixed voltage, have provided a detailed understanding of the sequence of changes in sodium and potassium channel activity that give rise to action potentials. - Voltage Clamp Method - control voltage and measure current
Method used to indicate how membrane potential influences ion current flow across the membrane

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14
Q

How do we calculate this relation of voltage to ionic current?

A

Ohm’s Law states that current (I measure in amperes or amps amount of current (A)) through two points with a resistor (R) in between is directly proportional to voltage (V) across the two points.
When it comes to biological membranes, current flowing through channels is proportional to the voltage across the membrane

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15
Q

Conductance

A

Conductance is I/R (inverse) - the higher resistance and lower conductance
If conductance is voltage independent the line will be linear - Leak channels always open so the conductance through our leak channels does not depend on village so leak channel IV plot will be linear

Leak channels always open so the conductance through our leak channels does not depend on village so leak channel IV plot will be linear - ion channel only allow one ion line will cross the voltage line at its equilibrium potential

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16
Q

Reversal Potential

A

When examining current-voltage (I-V) relationships, the membrane voltage at which the direction of current changes from negative (i.e., inward) to positive (i.e., outward) is called the reversal potential (Vrev).
The reversal potential simply refers to that membrane voltage at which there is no net current across the membrane (i.e., I = 0). Thus, at Vrev, there is no net ionic movement across the plasma membrane.
Not net flux of ions - 1=0, V=equilibrium potential(zero net flux across the membrane of ions so zero current) → reversal potential → direction of ion flow changes

Reversal Potential(not net flux of ions across membrane so when does the ion flow into or out of the cell) = Equilibrium potential

17
Q

voltage independent?

A channel that allows more than one ion channel through like ?

Cations:

Anions:

A

Iv plot is conduction through through the channel so the ions moving through channel at different voltages

So ligand channel not dependent on voltage has a linear relationship between current and voltage the conduction is not affected - voltage independent

A channel that allows more than one ion channel through like NMDA receptors allow Ca, K, Na

Cations: negative voltage is flowing inwards

Anions: negative voltage is flowing outwards

18
Q

What if conductance is not constant?

A

Think: what is an example of an ion channel that has conductance through the channel dependent on voltage?? VG K, Na, Ca - rapid decrease in voltage resistance when open then rapid increase in conductance - leak channel constant resistance always open

Here are examples of I/V plots when g is constant at all voltages tested, and when g(conductance) is dependent on voltage

Until gate opens not linear and after gates open linear

19
Q

I/V plot for NMDA receptors - are ligand and voltage gated
You can see the I/V plot slope changes depending on voltage when Magnesium ions are present, and that the I/V plot is linear when the neurons are in a Magnesium-free solution
Think: how does magnesium affect NMDAR function?

A

In the bath glutamate was present - experiments varied concentration of magnesium

In a magnesium-free solution with glutamate present glutamate binds to the NMDA receptor it opens and there is no magnesium present to block the pore so ions can flow through, we have removed the thing that makes it voltage gated

NMDA receptors unlike a traditional voltage gated channel that a voltage sensor that changes conformation at a certain voltage those wouldn’t be affected by this magnesium free solution bc they have a literal voltage gate

magnesium free solution our NMDA receptor glutamine opens then ions flow through when add magnesium the red line see voltage selectivity no longer a straight line until it reaches a certain level once we reach above zero that’s enough positive charge to kick out the magnesium above curve at right line

Has low amounts of conductance but then one rhea threshold we see increase conductance through the channel with the more positive we get

19
Q

What if a channel allows more than one ion??

A

The I-V curve for a channel specific for one ion passes through the voltage axis at the ion’s Nernst equilibrium potential: no net force, no net flow. This is considered the reversal potential.

If more than one ion can permeate a channel, the zero-current point for the channel’s I-V curve is the potential where the currents of the two ions balance to zero.

This potential will be a weighted average of the Nernst potentials for the permanent ions.

The weights are related to the conductances of the channel for each of the ions. If one ion predominates in terms of conductance, then the zero-current point will be close to that ion’s Nernst potential.

20
Q

Comparison of I/V plots for different Channels
I/V plots for AMPARs, NMDARs, and GABAaRs

A

AMPA and NMDARs are cation channels that are ligand-gated voltage independent

NMDAR is also voltage-gated due to the presence of magnesium voltage dependent

GABARs are chloride selective and ligand-gated