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5115 > Cellular Neurophysiology > Flashcards

Cellular Neurophysiology Flashcards

1
Q

the environment around the membrane when neurons are polarized and depolarized

A

Convention states the inside -70 (or -90) mV whereas the outside is 0 and this condition is defined as polarized.

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2
Q

What is the mechanism by which a negative resting membrane potential is generated?

A

K+ leaks out and Na+ leaks in but because there are less Na leak channels and therefore lower Na+ permeability, more K+ leaks out than Na+ leaks in. Negative ions can’t leak out because they are fixed to large proteins. As K+ ions leave, membrane potential becomes more negative

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3
Q

Electroneutrality

A

Neurons are very permeable to K+ because they contain an abundance of K+ leak channels and because there is a large outward K+ gradient and leak channels for K+, K+ diffuses out of the neuron. As K+ leaks out, inside face of the membrane is relatively negative, and the outside face is relatively positive. However, ECF and ICF are overall neutral, such that even though charges are separated at the membrane, the cell follows the principle of electroneutrality.

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4
Q

How is gradient (steady state) maintained in the face of leaking ions?

A

Potassium is leaking out and even though sodium permeability is low, sodium is still leaking in along a tremendous chemical and electrical gradient. The concentration gradients are maintained by ACTIVE TRANSPORT in the form of the Na+/K+ pump. Because 3 Na+ are pumped out and 2 K+ are pumped in, the pump is electrogenic, meaning it contributes slightly to Em (3 or 4 mV). The Na/K pump prevents dissipation of gradients, is fueled by ATP hydrolysis and is driven by internal Na+ concentration.

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5
Q

Goldman-Hodgkin’s-Katz equation

A

the greater the concentration difference of a given ion (i.e the gradient across the membrane) and the greater its membrane permeability, the greater will be its role in determining the membrane potential.

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6
Q

concentration gradient -70 mV

Na+

A

Into cell

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7
Q

Electrical gradient -70 mV

Na+

A

Into cell

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8
Q

Concentration gradient 30mV

Na+

A

Into cell

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9
Q

Electrical gradient 30 mV

Na+

A

Out of cell

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10
Q

Electrical gradient -70 mV

K+

A

Into cell

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11
Q

concentration gradient -70 mV

K+

A

Out of cell

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12
Q

Electrical gradient 30 mV

K+

A

Out of cell

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13
Q

Concentration gradient 30 mV

K+

A

Out of cell

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14
Q

Electrical gradient -70 mV

Cl-

A

Out of cell

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15
Q

Concentration gradient -70 mV

Cl-

A

Into cell

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16
Q

Electrical gradient 30 mV

Cl-

A

Into cell

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17
Q

Concentration gradient 30 mV

Cl-

A

Into cell

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18
Q

Electrical gradient -70 mV

HCO3-

A

Out of cell

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19
Q

Concentration gradient -70 mV

HCO3-

A

Into cell

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20
Q

Electrical gradient 30 mV

HCO3-

A

Into cell

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21
Q

Concentration gradient 30 mV

HCO3-

A

Into cell

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22
Q

Electrical gradient -70 mV

Anions

A

Out of cell

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23
Q

Concentration gradient -70 mV

Anions

A

Out of cell

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24
Q

Electrical gradient 30 mV

Anions

A

Into cell

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25
Q

Concentration gradient 30 mV

Anions

A

Out of cell

26
Q

Electrical gradient -70 mV

Cations

A

Into cell

27
Q

Concentration gradient -70 mV

Cations

A

Into cell

28
Q

Electrical gradient 30 mV

Cations

A

Out of cell

29
Q

Concentration gradient 30 mV

Cations

A

Into cell

30
Q

Equilibrium potential

A

The point at which the positive charges the accumulate outside the membrane repel the further outward movement of K+ along its concentration gradient

31
Q

Under what conditions would a neuron achieve an equilibrium potential for a given ion?

A

Cell must be permeable to that ion

Must have a gradient

32
Q

values for the equilibrium potentials of Cl

A

-87mV

33
Q

values for the equilibrium potentials of Na

A

+61mV

34
Q

values for the equilibrium potentials of Ca

A

+112

35
Q

values for the equilibrium potentials of K

A

-94 mV

36
Q

Which of the equilibrium potentials is the best predictor of the RMP?

A

K+ because of leak channels

In other words, the permeant ions with huge transmembrane gradients influence the membrane potential the most.

37
Q

If the permeability for K/Na/Cl/Ca increases - what is the result in each case?

A

K - flow increases (cell becomes more +)
Na+ - flow increases (cell becomes more +)
CL- - not much change
Ca - a lot of change

38
Q

How does a cell change it’s permeability?

A

Opening and closing channels

39
Q

Permeability Na+

A

0.04

40
Q

Permeability K+

A

1.0

41
Q

Permeability Cl-

A

0.45

42
Q

Why do we say Cl- is passively distributed?

A

It is free to diffuse in or out of cells because it is not affected by the Na+/K+ pump.

43
Q

If a neuron received a small depolarization or hyperpolarization, explain how the movement of Cl- would respond.

A

the Nernst calculation for Cl that Cl- is in (or nearly in) equilibrium across cell at rest. Because Cl- is passively distributed, when the cell is depolarized slightly, Cl- diffuses in and returns the potential to rest. When the cell is slightly hyperpolarized, Cl- diffuses out and returns the potential to rest. For this reason, increased chloride permeability stabilizes (or hyperpolarizes) the RMP

44
Q

What is the difference between conductance and permeability

A

Permeability depends on state of membrane whereas conductance depends on both state of membrane (# of open channels) and concentration of surrounding ions.

45
Q

Conductance

A

ease with which ions move through a channel.

46
Q

How can an ion channel be a resistor and a conductor at the same time?

A

A membrane potential is like an ionic battery in which the value of the battery is determined by the concentration difference of the ions and the number and kinds of channels that are open. The presence of channels increases conductance of membrane and increases ways for current to flow. A channel is not as good a conductor as free ions in solution. Because it has a narrow diameter, 0.6 nm, it acts like a resistor to ion passage. Each channel can be thought of as both a conductor and a resistor

47
Q

local current flow

A

As positive current enters the neuron, it will passively flow towards areas that are relatively negative. When current flows or diffuses passively it is called local current flow

48
Q

Compare and contrast the properties of local current spread and action potentials. Where, in terms of the anatomy of a neuron, are these types of activity found?

A

Local Current/Graded Potential:
Excitable cells cause current to flow by taking advantage of ion gradients and either opening or closing ions channels. For example, if there is an inward gradient for Na+ and Na+ channels are opened, Na+ will enter the neuron bringing positive charge with it. As positive charge enters the neuron, the RMP gets less negative and the neuron is depolarized. Keep in mind that local current flow is subthreshold. It is a localized depolarization that spreads out from a small area and decays as it spreads. Graded potentials decay over time. Graded or local potentials are important at the cell bodies and dendrites of neurons.

Action potentials have very different properties from graded potentials in that they are a propagated, self renewing current flow that is above threshold, they do not decay as they spread, and they travel the entire length of an axon.

49
Q

What are the events that lead action potential (AP) generation?

A

Depolarization - upon stimulation of a nerve cell by synaptic activity, positive charge enters the cell, depolarizing it and making the Em less negative and depolarization is the signal for opening fast v-gated Na+ channels. If a threshold potential (-65 to -30 mV) is reached, 1) fast v-gated Na+ channels will open, Increasing Na+ permeability and conductance. These two steps repeat in a positive feedback mechanism. The membrane potential will reach a positive value (+10 to +45mV). An all or none phenomenon, a positive spike on a voltage scale occurs and is called an action potential (AP).

a. As soon as they open, Na+ channels inactivate, decreasing the conductance of sodium. Inactivated channels are locked shut.
b. Depolarization is also the signal for opening slow v-gated K+ channels, but the results of increasing K+ conductance and permeability is not seen until Na+ channels inactivate.

50
Q

What events occur during an AP?

A

Depolarization, threshold potential, repolarization

51
Q

Distinguish between the mechanisms of the absolute refractory period versus the relative refractory period.

A

Period during which an excitable cell cannot be activated by a typical stimulus 1. Absolute - no stimulation will result in an AP because the Na+ channels are already open or inactivated 2. Relative -need greater than normal stimulus to cause AP because K+ channels are open. Action potentials triggered at this time may be a bit smaller because not 100% of the Na+ channels are back to the resting state. WAIT A MINUTE! Does this violate all or none? No, the neuron uses all available voltage gated Na+ channels; all or none is preserved.

b. The refractory period limits AP rate (transmission rate) - large fibers tend to have shorter refractory periods than smaller fibers and therefore tend to have higher transmission rates c. 500 to 1000 AP per sec - these are actual maximum rates that have been recorded

52
Q

Repolarization

A

Occurs after the Na channels inactivate and the K+ channels have had a chance to open fully. K+ exits the cell, making the neuron more negative. As K+ flows out (note, this is only a few ions) the Em returns to -80 mV or -90 or whatever RMP is. As the Em becomes more negative the 3D protein structure of the fast Na+ channels reset and close so that, should another AP occur, they can be activated again. In CNS neurons, the Em hyperpolarizes to a level that is more negative than the RMP because the slow K+ channels take time to close. This called the afterhyperpolarization and makes the neuron relatively refractory to additional stimulation.

53
Q

What does it mean to capitalize on the Na and K gradients?

A

Capitalizing on the Na+ and K+ gradients enables a neuron to be turned on and off very rapidly. At RMP, there is both an electrical and concentration gradient for Na+ to enter whereas at peak depolarization, there is both an electrical and concentration gradient for K+ to leave

54
Q

Explain how myelinated axons use both propagated current and local current flow to move an AP quickly along the axon.

A

Myelin essentially insulates the axon such that membrane resistance is much greater than axial resistance. In other words, current spreads down the lumen of the axon instead of leaking back out through the membrane. Action potentials are regenerated at the nodes of Ranvier between areas of myelination making this process fast and energy efficient.

55
Q

Speed of conduction depends on:

A
  1. axial resistance or the size of an axon
  2. the presence of myelination Increasing axial resistance (inner radius getting smaller) slows spread of current down the lumen of the axon.

As a result, larger diameter axons tend propagate action potentials faster, they also tend to be myelinated.

56
Q

How do demyelinating diseases change neuronal function

A

affect action potential propagation. Examples include multiple sclerosis, Guillain - Barre syndrome,

57
Q

Electrical synapse

A

Electrical synapses or gap junction allow cytoplasmic continuity because they span and connect two cell by channels composed of a protein called connexin. The connexin channel from one presynaptic membrane attaches to the connexin of a postsynaptic membrane, bringing the two membranes approximately 2 nm apart. Ions and other small molecules can flow along an electrochemical gradient from one cell to another. Local current flow is the mode of signal transmission. Gap junctions have a short synaptic delay as compared to chemical synapses and are bi-directional. Gap junctions are abundant between smooth and cardiac cells, less so in the CNS.

58
Q

Chemical synapse

A

use a neurotransmitter (NTX) released from presynaptic cells as the mode of signal transmission to a postsynaptic cells. Because the release of NTX and the response to the NTX are so specialized, chemical synapses are unidirectional. The synaptic delay is longer (3-5 msec) and the distance between pre and post synaptic membrane is longer (30-50 nm). There is no cytoplasmic continuity. The mediating agent, a chemical neurotransmitter, is synthesized in cell body by ER and Golgi, packaged in vesicles, transported down axon along cytoskeleton and stored in the axon terminus prior to release. Vesicles are stored at the presynaptic membrane with the help of docking proteins (eg. SNARES and synaptogamins). By-products are taken back up axon and sent in a retrograde fashion back to the soma.

59
Q

EPSP

A

Excitatory Post Synaptic Potential = Depolarization

i.e. Glutamate

60
Q

IPSP

A

Inhibitory Post Synaptic Potential = Repolarization/Hyperpolarization
i.e. GABA, opening up K+ or opening up Cl- channels

5115 (8 decks)

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