Psych 115 Week 3

Equilibrium potential for sodium

+ 50 mV

Resting potential

- 70 mV -> dominated by potassium

Resting potential

- 70 mV and the cell is said to be polarized

Equilibrium potential for potassium also called potassium battery

- 80 mV

Equilibrium potential of Cl-

- 80 mV

Permeability equal for na+ and K+

-15 mV

Duration of AP plus refractory period

1-2 msec and about 500 spikes/second

Stronger stimuli

1. Activate a greater number of receptors 2. Trigger a greater frequency of action potentials in sensory neurons Higher frequency, more, Action Potentials

5 concepts of electrophysiology

1. Diffusion of uncharged species 2. Diffusion of an ion 3. Equilibrium potential 4. Membrane potential 5. Action potential

Summary of electrical conduction

1. Diffusion: net flux from region of high concentration to region of low concentration due to random thermal motion 2. Diffusion of a charged molecule (unaccompanied by a counter ion) down its concentration gradient creating charge separation and an electrical potential 3. Equilibrium potential: flow of charge due from high to low concentration creates an electrical potential that drives a balancing flow of charge hence net flux = 0 4. Membrane potential: the weighted sum of equilibrium potentials, weighted by relative permeability 5. Action potential: flipping from one permeability state (dominated by K+) to another (dominated by Na+) and back

Many types of channels

1. Leakage channel: give resting potential 2.Voltage-gated Na+ and K+ channel 3. Ligand-gated channel: opened by NT, many are multi-subunit and several genes are involved in channels 4. Internal transmitter/messenger: bind to NT on inside instead of outside sometimes 2nd messenger and opens channel

Reason membrane potential falls

1. Na+ channels close on their own 2. K+ channels open 3. Membrane potential falls and the voltage is less inviting so Na+ close and K+ close

What determines the amount of depolarization?

1. Number and placement of excitatory inputs, the amount of excitatory transmitter, and the nature of the receptors 2. Number and placement of inhibitory inputs, the amount of inhibitory transmitter, and the nature of the receptors

What does myelin do?

1. Reduced capacitance of the axon membrane (how many mV you get for how many charges) -> need fewer charges to get same mV -> with fewer ions needed to depolarize less energy is required 2. much less leakage 3. charge in membrane potential conducted more rapidly Reason vertebrate brains can be packed with small neurons

Stages of action potential

1. Resting potential - 70 mV (open K+ and closed Na+ channel) also leak channels open 2. Depolarization when Na" voltage channels open 3. Repolarization when Na+ voltage gated channels close and slow to open K+ voltage gated channels open 4. Hyperpolarization (below resting potential, refractory period where cannot fire another potential)

What factors determine whether more Na+ enters than K+ leaves?

1. The amount of depolarization, which determines the number of open Na channels 2. The number of open K+ channels (Slow depolarization gives time for more of them to open) 3. The driving force on Na+ vs. the driving for on K+

2 ways to think about the membrane potential when permeabilities change

1. refer to the permeability ratio -> permeability to Na+ increases during depolarization 2. some current that charges into or out of the cell in order to rest the balance of + and -

What closes Na+ channels?

1. self inactivation 2. Voltage falls many neurons do not have Na+ inactivation and what brings potential down is K+ opening

Dielectric limit

100,000 Volts/cm Change in membrane potential by 5 mv is huge -> causes a change in the shape of proteins in the membrane

Equilibrium potential of Ca+2

2-4x + 29 mV

K+ higher inside Ek = -80 mV and membrane potential is 40 mV calculate driving force?

40 + 80 = 120 mV out of the cell

How thick is the neuronal membrane?

5 nm

Na+ greater outside Ena = 50 mV and membrane potential is - 70 mV calculate driving force?

50 + 70 = 120 mV into the cell

Voltage clamp

A device that enables an investigator to hold the membrane potential constant while transmembrane currents are measured. By negative feedback, any difference between the 'command voltage' and the measured voltage is countered by a current that can be measured, a current that is equal and opposite to that flowing into or out of the cell. Thus, the clamp controls voltage and measures current.

Threshold

A few Na channels open when the membrane becomes slightly depolarized from the resting potential Due to these newly opened Na channels. more Na+ enters than K+ leaves and the membrane becomes slightly more depolarized Not constant: Voltage gated Na+ and K+ channels have the same voltage dependence -> if both open nothing happens -> if bring the threshold up slowly to normal threshold (-65 mV) some Na+ channels will open but K+ channels will open too, now have to depolarize more to overcome increase K+ so the threshold will go up

How long does action potential take?

About 1-2 milliseconds

Refractory period

After excitation, membrane is refractory to firing another action potential because the K+ permeability is still so high that openings of Na channels cause negligible depolarization After-hyperpolarization: membrane falls closer to the equilibrium potential for K+ (-80 mV) below normal resting potential (-70 mV) Absolute: closing Na+ channels and open K+ channels Relative: hyperpolarization -> can overcome with a strong stimulus

Why does not AP travel backward?

Because the backward axon is in the refractory period -> membrane just fire AP and it is in refractory since K+ is open so not going to fire another AP -> so AP conduction in just one forward direction

Saxitoxin (STX)

Blocks voltage-gated Na+ channels found in red tide and puffers

Equilibrium potential of the outside of the cell

By convention outside is always assigned the value 0

Nerst Equation

Calculates equilibrium potential: A potassium equilibrium potential exists when electric charge that develops across the membrane is sufficient to prevent net diffusion of potassium ions down their concentration gradient. This potential can be calculated with the Nernst equation. EK = 58 mV log [K+]out/[K+]in

What is a genetic abnormality of an ion channel called?

Channelopathy

Patch clamping

Collect a single channel (single molecule) to study by attaching a small patch of membrane to the tip of a glass micropipette Found: depolarization of the membrane cause most Na+ channels to open, and single channel spends more time in open state than closed state in depolarized state and more time closed at lower membrane potential. Explains the voltage gated dependence on the basis oof what a signle channel does

What determines the driving force?

Concentration gradient and membrane potential -> electrochemical -> where electro is equal to the battery and chemical is membrane potential

How to calculate driving force

Distance from Na+ or K+ from actual membrane potential -> always positive if at - 70 mV: driving force of Na+ -> 50 + 70 = 120 mV into cell driving force K+ = 80 - 70 = 10 mV out the cell if +40 mV: driving for Na+ -> 50 - 40 = 10 mV into cell driving for K+ -> 40 + 8- = 120 mV out of cell

Refractory period

During hyperpolarization when cannot fire action potential also relative refractory period where action potential could be forced

Tetrodotoxin (TTX)

Found in Japanese puffer fish and blocks voltage-gated Na+

Batrachotoxin

From skin of frogs Forces Na+ channels to stay open used as poison dart

What used to study action potential?

Giant Axon of a squid

Larger axons

Have a higher conduction velocity Some entering Na+ ions depolarize the forward neighboring patch of membrane, but some leak back across the membrane It is easier for ions to travel down a larger tube than a smaller tube, so the proportion of ions that remain inside the axon and depolarize it is greater in a larger axon With more ions in forward patch it depolarizes more quickly and conducts AP at higher velocity

Use of electrode to measure resting potential

Have electrode outside the cell and reference electrode in a bath and stick it into the cell and use it to measure the resting potential relative to outside it and measure - 70 mV

Inward and outward currents

Hyperpolarization -> not much change in current Depolarization -> see current going inward then outward -> electrical current flows in then out and inward current is early and the outward current is late

Location of EPSPs and IPSPs relative to axon hillock

If nearer then more powerful than further synapses Inhibitory close to axon hillock and shut down AP even at face of all excitatory further away -> position of synapse important Synapses closer to the cell body generally have greater influence on the axon hillock because currents and potentials decrease as they spread passively (electronic conduction) from synapses

Inside of equilibrium potential for sodium

Inside will be positive and outside 0

Magnitude of currents: voltage dependence

Inward current carried by sodium and the outward current is carried by potassium Conductance of Na+ channels increase as depolarize and conductance of K+ channels increase as depolarize -> roughly same voltage dependence

Selectivity filter

K+ channels are lined with oxygen atoms that mimic water molecules Unhydrated K+ ions pass through this selectivity filter easily than Na+ -> because Na+ hydrated by coat of water that makes it bigger than K+ and the negative oxygen surrounding the channel can replace the water on K+ to strip the water and let it through

Inside of equilibrium potential for potassium

K+ moves out of cell so inside becomes negative and outside zero

Why do potassium channels with the same voltage as Na+ channels do not open?

K+ voltage gated channels are slow to open and by the time the action potential gets to the peak they open up and this brings to the membrane potential down because the increasing K+ permeability and Na+ channels start to close as the membrane potential falls

Phospholipid

Made up of a glycerol backbone (3 carbons), hydro-carbon tail, and phosphate (negative) choline (positive) head group Have two hydrophobic hydrocarbon (oily) tails Hydrophilic phosphate head

Depolarization

Membrane permeability to Na+ (pna+) increased and Vm rises from -70 mV too a less negative value the peak value is +40 mV where Pna = 12 and Pk = 1 net entry of Na+ ions causes a positive change in electrical potential of the interior, making it less negative (depolarizing it)

What makes sodium channels open?

More sodium channels open as membrane potential becomes depolarized because the sodium channels are voltage-dependent -> sodium channels open when the membrane potential rises (depolarizes) Threshold: when the potential goes to a point where more sodium enter than K+ leaves All-or-nothing: more K+ go out than Na+ so do not get more positive -> have to open enough Na+ channels so Na+ entry exceeds K+ exit

Concentration of Na+, K+, Cl-, Ca2+, and Proteins inside and outside cell

Na+ -> more outside than inside K+ -> more inside than outside Cl- -> more outside than inside Ca2+ -> more outside than inside proteins -> more inside than outside (ions of K+ roughly equal inside cell due to the proteins) + and - outside are equal to inside

How do the ions move?

Na+ into the cell (inside becomes positive) K+ out of the cell (inside becomes negative) Cl- into the cell (inside becomes negative)

Stick electrode in cell what do we measure?

Na+ more outside, K+ more inside -> membrane more permeable to K+ than Na+ so membrane potential is negative

Hyperpolarization

Net exit of positive ions, K+, that causes Vm to become more negative than resting potential Net entry of Cl- also causes hyperpolarization Competes with depolarization reducing or preventing another action potential -> so described as inhibitory while depolarization described as excitatory

What makes potassium channels open so they dominate the late phase of action potential?

Open when membrane depolarized and have similar voltage dependence as Na+ but they open more slowly than the Na+ channels open If open at same time there would not be an action potential

Release of a neurotransmitter at a synapse could cause an EPSP in the postsynaptic dendrite by

Opening ligand-gated na+ channels

An IPSP would be produced by the

Opening of ligand-gated k+ channels Closing of ligand-gated Na+ channels opening of ligand-gated Cl- channels

Synaptic communication

Presynaptic terminal (at end of neuron at axon terminal) synapses with postsynaptic terminal (start of other neuron at dendrite) Stained with heavy metals, such as lead or uranium, to see cell membrane where Ramon y Cajal could not see but had to only infer

Why does diffusion occur?

Random thermal motion where things end up moving from region of high concentration to low concentration

Temporal summation

Repeated firing of a presynaptic neuron produced repeated EPSPs in the same postsynaptic spine, giving summation in time but not over different places -> involves single synapse EPSPs in quick succession in time can cause AP to fire

Electrotonic (passive) conduction

See less and less depolarization as go down the axon from where stimulation occurred -> signal decays over the distance The greatest amount of depolarization happens right where stimulate it -> less as get further away from it Due to leakage across the axonal membrane where you lose pluses so voltage goes down fix by increasing axon size or coat membrane in oil by myelin

What makes Na+ channels close?

Since voltage dependent they close as membrane potential falls to its resting value open channels close (inactivate) after a while even at depolarized membrane potential

Mechanism of conduction of the AP

The Na+ ions that rush in during an action potential depolarize the forward neighboring patch of membrane and cause an AP to arise there as well

How the phospholipid layers form?

The hydrophobic fatty acid tails and hydrophilic polar heads are part of the lipid bilayer. The tails repel water, so they are always facing the inside of the membrane. The polar heads love it, so they face the outside of the membrane. tails -> away from water head -> associate with water oily tails toward center and hydrophilic head groups face outside

What causes depolarization?

The influx of sodium due to the opening of sodium channels Extra permeability to sodium causes the membrane potential to rise which causes more sodium voltage gated channels to open which causes the potential to rise even higher -> this causes the ratio of pNa+ > pk+ -> until all voltage gated sodium channels to open and now at the 40 mV peak

Hyperpolarization

The movement of the membrane potential of a cell away from rest potential in a more negative direction The ratio of Pk to Pna is higher than at rest -> goes closer to potassium batte

Membrane potential (Vm)

electrical potential of the cell's interior relative to the exterior (which by convention is assigned the value 0)

Spatial summation

excitatory and inhibitory synapses are distributed in space, typically widely spaced receptor clusters on dendrites near the cell soma Adding EPSPs and IPSPs in space -> if depolarization of EPSPs exceed hyperpolarization of IPSPs cell will fire AP -> sum up at synapses

EPSP

excitatory postsynaptic potential: fast or slow Opening of Na+ channels or opening of unselective channels (-15 mV) would depolarize the cell

If Pna+ = 12 and K+ = 1 what is membrane potential?

in reference to K: (1/13)*130 = -10 Ena+ = 50 50 - 10 = +40 mV (at peak) Because mainly permeable to Na+ but a little bit of permeability to k+

Permeability is 11 for K+ and 2 for Na+ what is membrane potential?

in reference to Na+ = (2/13)*130 = 20 -80 + 20 = -60 mV

IPSP

inhibitory postsynaptic potential: Fast or slow Opening of K+ or Cl- channels would hyperpolarize the cell Inhibit with increasing overall permeability,m the effectiveness of Na+ channels opening would be reduced away from the threshold An increase in permeability would mean the effectiveness of EPSPs going to be smaller/reduced -> IPSPs make EPSPs smaller

Diffusion

molecules move from high to low concentration

Neurons can compute

neuron receive 1,000 or more synaptic inputs but only produce on output (AP) Addition/substraction: IPSPs and EPSPs respond to the logarithm of input -> input of 10 gives an output of 1 Add log -> multiplication Substract log -> division Boolean Algebra -> neuron can do logical operation like a computer

Axon Hillock

not myelinated where decision to fire AP occurs Critical area for deciding to fire not myelinated and has many voltage-gated ion channels

What can pass the phospholipid bilayer?

only hydrophobic small molecules Cannot pass -> water, sugar (glucose), ions (charged), amino acids

Repolarization

return. too resting potential

Graded potentials

small changes in membrane potential that by themselves are insufficient to trigger an action potential Small stimuli both hyperpolarizing and depolarizing produce graded potentials -> while stronger depolarizing stimuli trigger AP and at a higher frequency

If voltage gated potassium channels were not slow to open what would happen?

the action potential would go nowhere

Molecular basis of voltage dependence

the change in the dielectric constant 10,000 volts/centimeter causes the channel to open where the increasing positive membrane potential causes the opening of the channel

Saltatory conduction

the jumping of action potentials from node to node -> patches of plasma membrane not covered in myelin giving conduction speed of 100 meter/second or greater

Myelin and nodes of Ranvier

Vertebrate have myelin (oily) -> around axon and allows for less leakage of ions Breaks in myelin -> nodes of Ranvier where all voltage gated channels located so better able for charge to come into the axon and up to next node

Potassium activiation

Vm falls from peak because K+ channels open and Na close.

EPSPs and IPSPs

always ligand gated channels

Giant quid axon

big/thick axon conduct AP faster due to less leakage 0.5-10 mm used for escape reflexes

logs

count the zeros of the ratios 10,000 -> 4 1000 -> 3 100 -> 2 10 -> 1 1 -> 0 When do K (out/inside) more on inside but just flip ratio and add negative

phopholipid bilayer

Two layers of phospholipids -> two molecules thick head groups directed outward and interacts with surrounding water and tails packed into the interior

Relative permeability

At rest permeability of K+ > permeability of Na+ At rest: Pk = 12 and Pna = 1 total 13 130 (1/13) = 10 -80 + 10 = -70 mV (resting potential)

Equilibrium Potential

Consider sodium ions. [Na+]out > [Na+]in 1.If the membrane is permeable to Na+, then more Na+ enters from the outside than leaves from the inside. 2.The inside develops a net excess of + charge over - charge. 3.The excess + charge inside acts like 'pressure' against the entry of more + ions, including Na+. This electric pressure is measured in millivolts (mV), positive inside with respect to outside. (By convention, the outside is always assigned the value 0.) 4.The excess of + charge inside (and the positive voltage it generates) increases up to the point that the rate of the efflux of Na+ (due to the positive voltage) from the interior equals the rate of influx (due to the concentration gradient) into the interior. 5.The potential across the membrane at this point is called the equilibrium potential for sodium (ENa). If the interior became even more positive, then more Na+ would leave than would enter, and the potential across the membrane would respond by falling back to the equilibrium potential for sodium (ENa). rate of entry equals rate of exit -> equilibrium the point at which the movement of ions across the cell membrane is balanced, as the electrostatic pressure pulling ions in one direction is offset by the diffusion force pushing them in the opposite direction

Size of AP down axon

The size of the AP is the same at each point along the axon because AP are all or nothing when depolarize part of axon some of the positive ions push along the axon to got to the next area on the axon

sodium-potassim pump

The sodium-potassium pump takes K+ ions in and pushes Na+ ions out, replenishing normal ion gradients. Ion channels allow K+ ions to leak out, leaving behind unbalanced negative charges, leading to the resting potential. Uses ATP and 40% of the body used to drive pump. Replenishes gradient

membrane potential

The voltage across a cell's plasma membrane.

How is membrane potential measured?

The weighted sum of two equilibrium potentials of K+ and Na+