Neuro Unit 2

What is the difference between action potential and graded potential?

Action: long distances

Graded: local membrane changes only

What are the ions inside and outside of the neuron at resting potential?

Outside: Na+, Cl-, and Ca 2+

Inside: K+, and anions such as proteins, organic phosphates, and other components in the cytosol

What is the Resting Membrane Potential, the point of no return, max positive point, and lowest hyper polar state?

RMP is -70 mV (or -65)

Threshold: Once potential is -55 mV, action potential is kicked off

Potential raises until +30 mV

Repolarizes and Hypopolarizes to -90

Returns to RMP at -70 for next action potential

What three factors contribute to RMP?

\-concentration of ions differing from the inside and outside

\-membrane permeability difference between Na+ and K+ (More K+ permeability)

\-Na/K pumps more Na+ out of cells than K+ enters

Describe the neuron at resting membrane potential?

Na+ 150 mM outside cell

Cl- 150 mM outside cell

K+ 100 mM inside cell

So the total difference is -65 mV

Explain how RMP is maintained

Na+ leak channels bring ions inside

K+ leak channels bring ions out, but way more than Na+ channels do.

This happens till both concentrations are at equilibrium

The Na+/K+ ATPase brings 2 K+ in and 3 Na+ out so that the inside can still be more negative.

What is the NERNST equation and what does it do?

The equation to calculate equilibrium potential in each ion alone

What is equilibrium potential for Na+ in a neuron at RP?

\+60 mV

What is equilibrium potential for K+ in a neuron at RP?

\-90 mV

What is equilibrium potential for Ca 2+ in a neuron at RP?

\+130 mV

What is equilibrium potential for Cl- in a neuron at RP?

\-70 mV

When the voltage of the membrane is more positive than E(K+) which is -90 mV, the K+ ions flow. . .

out of the cell to make Vm more negative

When the voltage of the membrane is more negative than E(K+) which is -90 mV, the K+ ions flow. . .

into the cell to make Vm more positive

What is the Goldmann-Hodgkin-Katz equation and what does it do?

GHK takes the differences in distribution and permeability of all ions into account to find the Vm. Can omit the Cl - p and concentrations.

No z is taken into account because the Cl- is reciprocal.

Action potentials

Action potentials can travel long distances

Caused by depolarization, then falls to repolarization.

Voltage gated channels open in sequence. all or nothing.

If a stimulus reaches threshold, the action potential stays the same, no stronger or weaker impulses

Graded potentials

Local membrane change

Vary in amplitude depending on the strength of the stimulus.

Depolarization or hyperpolarization causes.

Occur in dendrites and cell body

What is voltage?

Potential difference in charge between two points in an electrical field.

Used to present membrane potential since there is difference in charge between the inside compared to the outside.

What is current (I)?

the flow of charge. Rate at which charge flows past a point in a circuit. Must have voltage (difference) to flow.

Hodgkin, Huxley, and Katz found what?

Action potentials results from transient charges in the permeability of the axon membrane to sodium and potassium

At resting membrane potential. . .

\-70 mV:

The dominant leak channel is the K+ for Resting Membrane potential.

At the depolarizing phase. . .

Chemical or mechanical stimulus caused by some graded potential brings the voltage to -55 threshold.

Voltage gated Na+ channels are more sensitive, open first and Na+ rushes into the cell.

The depolarizing phase brings the voltage up to around +30.

At repolarizing phase. . . .

The voltage gated Na+ are closed by their inactivation gates and the K+ voltage gates open. The outflow of K+ returns membrane potential to -70 mV.

At the hyperpolarizing phase. . .

The K+ flow continues because of the equilibrium driving force bringing the potential towards the -90 equilibrium potential of K+. The voltage gated K+ channels close once the potential reaches -70 mV once again.

The Na+/K+ ATP pump helps restore the RMP.

Absolute Refractory Period

\-Even strong stimulus can’t restart action potential.

\-Na+ channel activation and inactivation period. Na+ channel must return to the resting state before an a.p. can happen there.

Basically the depolarizing and repolarizing phase

Relative refractory period

The hyperpolarizing phase is when the Na+ channels are reset and can work again but the K+ channels are still open.

A suprathreshold must occur to start an AP.

What are the three factors that affect the speed of propagation

1. More myelination increases the speed
2. Axon diameter: bigger diameter is faster
3. Temperature: higher temp is faster

Continuous conduction

When the fibers are unmyelinated, then each step down the axon is depolarization.

Saltatory conduction

Myelinated fibers:

depolarization only at Nodes of Ranvier where there are ion channels.

Current carried by ions flow from node to node

This is the faster and energy saving method

Lidocaine and Procaine work by. . .

Binding to the voltage-gated sodium channels. Lidocaine can’t gain access to the binding site from the outside so it has to cross the axonal membrane and then pass through the open gate (The Na+ gates are open more often) interfering with the normal Na+ flow.

Leakage (non-gated) channels

always open!

* more K+ leak channels than Na+
* selective permeability due to the amino acid residues that line the pore.

Ligand-gated channels

Open and close due to a stimulus, neurotransmitter. results in neuron excitability. Lots in the dendrite to take chemical neurotransmitter and begin propagation.

Voltage gated channels

responds to change in membrane potential.

Na+ channels are more sensitive and open before the K+ channels do. The Na+ channels also close with an inactivation right when the K+ channels open up.

Mechanically gated ion channel

respond to mechanical vibration or pressure results in opening and closing. Like touch

Why are GABA and Glycine receptors special?

Respond to chemical but are chloride channels, are anion receptors. They are the main inhibitory channels.

Depolarizing is excitatory

Polarizing is inhibitory

What are the properties of the Ca, Na, and K voltage gated channels?

Na monomeric (1 gene)

Ca monomeric single polypeptide too

K individual subunits from different genes for different receptor types. 4 tetramers

What is resistance?

rate of flow through space (slowness).

A cell is a resistor, cytoplasm slows spread of currents

Ion channels also behave as resistors, restricting the flow of ions in and out of cell

Resistors is series sum together

\

State Ohm’s law?

V=IR

What is conductance?

conductance (g) is the inverse of resistance 1/R

Conductance in series sum

\
can be considered the same as permeability, in GHK

What is patch clamp recording?

It allows us to study single or multiple channels in neurons. Developed by Erwin Neher and Bert Sakmann

You use a pipette to pierce a cell membrane

Cell attached

Pipette suctioned right onto the membrane and no more ions can flow in due to seal outside of the channel.

Only movement within a single channel is measured.

Inside out recording

When you pull the pipette off and take a piece of the membrane, the inside of the channel is now exposed and you can test how the inside would react to various changes.

To record single channel activity with access to cytoplasmic side of channel. can test things like Ca+ dependence, cytosolic second messengers, G-proteins

Whole cell recording

Stronger suction to make the cytoplasm continuous with the pipette interior. Your whole pipette simulates the continuing cell interior.

Record macroscopic changes from whole cell body

Outside-out recording

When you have the pipette pull the membrane with suction, cut sides can anneal together to reseal and flip the membrane. Now you can study how the channel interacts from the outside.

(ligand gating tests)

Voltage and V clamp reading

Up is depolarizing

Downward is polarizing (more negative)

A voltage clamp measures currents. Hold voltage steady using feedback sensor to record how much current is used

Current and Current Clamp reading

downwards is inward

upwards is outward

Current clamp measures voltage by injecting predetermined current to record voltage changes

Optogenetics

introduces into neurons foreign genes that express membrane ion channels that open in response to light.

What are examples of the ligand gated receptors?

nAChR cation channel

GABA anion channel

5-HT3 reacts to serotonin, Na and K

Glycine is anion channel

ATP P2x reacts to ATP

Binds to neurotransmitter glutamate and then to their selective chemicals:

NMDA

AMPA