Lecture 3.1: Neuron at Rest

Question 1

Membranes prevent the diffusion of charged molecules:

Membranes create a ______

Composed of ______

Prevent movement of ____, allow diffusion of ______, general anesthetics

Answer 1

Membranes create a barrier, delimit the cell

Composed of glycerophospholipids

Prevent movement of ions, allow the diffusion of amphiphillic molecules, general asthetics

Question 2

What structure allows the movement of ions across the plasma membrane of a cell?

Answer 2

Transmembrane proteins such as ion channels, transporters or gap junctions allow movement of ions

Question 3

Upon stimulus, ion channels can switch from a ____ state to an ____ state

Stimuli can include ______ or ______

This moves ions closer to their ______

Answer 3

Upon stimulus, ion channels can switch from a closed conformation to an open state

Stimuli can include changes in voltage of the presence of a ligand

This moves ions closer to their electrochemical gradient

Question 4

Transporter examples include ______ and ______ (both of which use ATP to move ions against their gradient)

_______ traverse the extracellular space, connecting the intracellular space of two adjacent cells, allowing small molecules to pass through

Answer 4

Transporter examples include pumps and exchangers; they use ATP in order to move ions against their gradient

Gap junctions traverse the extracellular space, connecting the intracellular space of two adjacent cells… allowing small molecules to pass through

Question 5

The two electrical components of a biological cell are ________ and ________

Explain their electrical equivalents

Answer 5

Lipid bilayer is like a capacitor (holds/stores charge)

Ion Channels are like resistors (allow things to go through them but slowly)

Question 6

What is the equivalent circuit of a biological membrane?

Answer 6

A simple/classic RC circuit

with a resistor (ion channels)

and a capacitor (lipid bilayer)

Question 7

What are the units for current?

Answer 7

Current is an Amphere (A) which is C/sec

or coloumbs per second

Question 8

Explain resistance in terms of pipes

What is conductance?

Answer 8

Resistance: narrower channels or pipes present GREATER resistance to flow

Conductance is the inverse of resistance (conductance is higher in wide channels)

Question 9

Explain capicitance

Answer 9

Capacitance is analogous to membrane surface area

Voltage changes slowly across a high capacitance membrane (water fills a large glass slowly)

Voltage changes rapidly across a low capacitance membrane

Question 10

Voltage changes slowly across a _______ capacitance membrane and rapidly across a _____ membrane

Answer 10

Voltage changes slowly across a high capacitance membrane and rapidly across a low-capacitance membrane

Question 11

Explain “Resting Potential” of a neuron

• Definition
• failure to keep it causes what?

Answer 11

Resting Potential:

• “DEFAULT” electrical potential on the neuron in the absence of any inputs
• Failure to keep the RP disrupts neuronal function

Question 12

Explain Subthreshold Potentials

Answer 12

Subthreshold potentials or “graded potentials” are electrical inputs that do not cause an action potential (AP) to fire

Other examples of these are EPSPs and IPSPs

Question 13

The Resting Potential of neurons is a result of…

Answer 13

Resting potential in neurons is a result of uneven distribution of charged molecules across the membrane

Question 14

The mechanism used by the neuron to maintain its Resting Potential determine that neuron’s _____

Explain

Answer 14

The mechanism used by a neuron to maintain the RP (during rest or when receiving inputs that deviate the membrane potential from the RP) detremine the neuron’s excitability

• Neurons that deviate easily from the RP are more excitable, they can reach threshold for an AP quickly
• Neurons that deviate briefly and rarely from RP are less excitable
• Two neurons with the same RP are not necessarily similar in their excitability, they can have different electrochemical mechanisms

Question 15

What is the range for the RP of neurons?

Answer 15

The resting potential (RP) of neurons is between

-50 mV to -70 mV

Question 16

What is the value of the Nernst Potential for the following ions:
Na

K

Ca

Answer 16

Ena = +60 mV

Ek = -90 mV

Eca = +120 mV

Question 17

What is the concentration of the following ions inside and outside of the cell:

Na

K
Ca

Question 18

Three ions move across the membrane at rest

Which three?

At steady state, the chemical and electrical forces are _________

Answer 18

Three ions move across the membrane at rest (K+, Na+, and Cl-)

At steady state, the chemical and electrical forces are equal and opposite to so that no net K movement occurs

Question 19

The Nernst equation calculates what?

What does Nernst potential indicate?

Answer 19

The Nernst equation calculates the electrical potential of a given ion

It has electrical and chemical contributions

For example, the nernst potential for K is -92 mV

At -92 mV ions are at a steady state, no net flux occurs

Question 20

What is the Nernst potential for K?

What happens when the system gets perturbed?

(What happens when the potential is more positive vs more negative?

Answer 20

Normally, K inside the cell is a lot higher (155 mM)

Nernst potential for K+ is -92 mV

Thus, at a more positive value than that, K+ will LEAVE the cell to make the inside more negative and shift back to equilibrium

At values more negative than that, K+ will enter the cell in order to bring in more positive charges and bring the potential back up to nernst

Question 21

If [K}outside increases

• what happens to the chemical gradient?
• What happens to the electrical gradient?

Answer 21

If [K] outside the cell increases (aka in hyperkelemia)

• the chemical gradient will be reduced
• The electrical gradient will increase

and then K+ ions will enter the cell until a new resting potential is achieved

Remember, this causes issues with firing APs

Question 22

The RP (resting potential) depends on the distribution of all permeable ions: (___, ____, and ____)

Eplain what the GHK equation calculates and accounts for

Answer 22

The RP depends on the distribution of all permeable ions: Na, K, Cl

The GHK equation is a more accurate way than Nernst to calculate/predict cell behavior in regards to membrane potential

Unlike nernst, GHK accounts for ion permeability

Question 23

What is the GHK equation?

What is the permeability of the following ions: Na, Cl, and K

Answer 23

GHK equation is shown in the picture below

Pk = 1.00 (60-70% at rest)

Pcl = 0.45 (or 25-35% at rest)

Pna= 0.004 or (3-4% of the current at rest)

Question 24

Explain the following Cl ion transporters:

NKCC

KCC

Answer 24

NKCC is a Na/K/Cl transporter that moves Cl ions INTO the cell

KCC is a K/Cl carrier that moves Cl ions out of the cell

Question 25

The RP is maintained by moving only _____ of the free ions in cells

A gradient must be maintained to keep the cell functioning normally, thus Na+ and K+ ions are ___________

Explain the Na/K ATPase

Answer 25

The RP is maintained by moving only 1/1000th of the free ions in the cells

A gradient must be maintained to keep the cell functioning normally, thus Na+ and K+ ions are “pumped” against their gradient, using energy, to keep those ion concentration differences inside and out of the cell

The Na/K ATPase hydrolizes ATP and pumps 3 Na out and 2 K+ in, thus causing hyperpolarization inside the cell

Question 26

What happens when you inhibit the sodium potassium ATPase?

Give some examples of substances that block this pump

Answer 26

The Na/K ATPase works in order to re-establish the gradient of Na high outside and K high inside (it pumps 3 Na out and 2 K+ inside, hyperpolarizing the inside of the cell/making the inside negative)

If you inhibit this pump, the membrane will depolarize

Examples of substances that do this are digitalis, ouabain, and digoxin. This causes paralysis, and can be used to treat irregular heartbeats

Question 27

Immature neurons lack what kind of Cl ion transporter?

What does that mean if you use GABA on immature neurons?

Answer 27

Immature neurons LACK a KCC

GABA is usually inhibitory neuron (usually moves Cl inside, hyperpolarizes the cell and makes it less likely to fire an AP)

BUT in immature neurons, GABA is excitatory (Cl will exit the cell)

Question 28

Synaptic Inputs:

Currents that cause depolarization are called ____

Currents that hyperpolarize are ______

Answer 28

Synaptic Inputs:

Currents that cause depolarization are called inward (example, inward Na or Ca influx)

Currents that cause hyperpolarization are outward (example, outward K or inwards Cl)

Question 29

What do nonspecific cation channels (like ionotropic receptors) do?

What is the Erev for ionotropic receptors?

Answer 29

Non-specific cation chanels like ionotropic receptors move Na in and K out (with a net inward, depolarizing current)

Erev (the reversal potential) for these = 0

Question 30

What is input resistance?

What are synaptic inputs?

Answer 30

Input resistance is the TOTAL resistance across a membrane, defined by the ion channels present in a cell. A high input resistance means those channels are closed.

Synaptic inputs are any signal that the neurons receive. Neurons constantly receive these synaptic inputs.

These inputs will cause either opening or closing of ion channels. This can result in :

1. Generation of synaptic currents
2. Alteration of input resistance

Question 31

A synaptic input affect’s a neuron’s excitability through changes in _____ and _____

Synaptic inputs are governed by Ohm’s Law which is _____

Answer 31

A synaptic input affects a neuron’s excitability through changes in input resistance and membrane potential

Synaptic inputs are governed by Ohm’s Law

V = I * R

(I is the capacitance, and R is the total resistance… aka all the ion channels)

Question 32

A synaptic input will cause a _____ current

That current will elicit a change in memrbane voltage that must follow Ohm’s Law and will therefore be proportional to the synaptic current multiplied by the imput resistance:

• The synaptic current is more effective at changing the membrane potential if _____

Answer 32

A synaptic input will cause a synaptic current

Due to Ohm’s Law (V= IR):

The synaptic current is more effective at changing the membrane potential if the R_input is high (AKA channels are closed)

The synaptic current is less effective at changing membrane potential if R_input is low (channels are open)

Question 33

Explain how synaptic inputs can be excitatory vs inhibitory

Answer 33

Synaptic inputs can be:

• Excitatory: (make neuron more likely to fire AP) usually cation influx and depolarization…. and in this cause the depolarizing synaptic currents dominate over the negative effect of R_input

_{To explain this: closure of K channels at rest results in cell depolarization, the input resistance increases and outwards K stops, causing net accumulation of positive charges in side}

• Inhibitory: they make the neuron less likely to fire an AP… outward K current or inward Cl current will decrease R_input therefore the synaptic current will have less impact… a hyperpolarizing current will also bring the resting potential to more negative values

Question 34

Excitatory Ionotropic Receptors:

What is the excitatory NT?

What are the receptors?

Answer 34

Excitatory Ionotropic Receptors:

Ligand gated GLUTAMATE receptors:

AMPA and NMDA…. both cause an EPSP

Permeable to cations

Summation of EPSP can cause firing of an AP

AMPA receptor:

• permeable to Na and K, reversal potential is O mv
• Na and K move with their gradients, cause a quick depolarization and fast return to resting potential

Question 35

Inhibitory Ionotropic Receptors:
What are the two inhibitory NTs

What kind of ion are the receptors permeable to?

What do they cause?

Answer 35

INHIBITORY NT is GABA or Glycine

The receptors are ligand-gated GABA or glycine receptors

They are permeable to anions

Cause an IPSP, which reduces the probability of firing an AP

GABAa receptor: permeable to Cl, reversal potential is -70mV

Question 36

Anions are unevenly distributed inside and outside the neuron:

Some molecules essential for life are negatively charged, they are abundant in the cell and do not exist outside:

1.

2.

3.

Answer 36

Some molecules essential for life are negatively charged, they are abundant in the cell and do not exist outside:

1. ATP and ADP
2. Nucleic Acids: DNA (nucleus). mRNA and tRNA (cytosol) usually bound to Mg
3. Amino Acids: glutamic acid and aspartic acid