Ch. 4; Cell anatomy and physiology - Part 2

Other examples

'tribo-' comes from the Greek word τρίβω (τριβή: friction, rubbing) Other examples - running a plastic comb through your hair - rubbing a balloon against your hair - rubbing a plastic pen on a sleeve of clothes made of cotton, wool or polyester Because both the amber and wool are now electrically charged (either negatively or positively), any contact with an uncharged conductive object or with an object having substantially different charge may cause an electrical discharge of the built-up static electricity, resulting in a spark. NB: Lightning is the result of triboelectric charging of ice and water droplets within clouds

How ion movement produces electrical charges

- Diffusion - Concentration gradient - Voltage gradient Multiple factors influence the movement of anions and cations into and out of cells

Electrical charge

- Electricity is defined as the flow of electric charge - Charge is a property of matter (just like mass, volume, or density) - Just as you can quantify how much mass something has, you can measure how much charge it has - The key concept with charge is that it can come in two types: positive (+) or negative (-)

Measuring electricity in the nervous system

- Equipment: potential differences (voltage) -> voltmeter electrical current -> ampere meter - Always 2 connections (poles)! -> e.g. if you use EEG to measure brain activity, you always have to have sort of reference point, and usually that's the thickest point of the skull which is located behind the scenes - For instance: inside versus outside of a cell (over the cell membrane) -> One creature that is frequently used for this is a squid -> large axons -> easy test subject

Part 2 - Cell anatomy and physiology

- Intermezzo: Electricity - Resting potential - Graded potential - Action potential

Recap: Part 1 - Cell anatomy and physiology

- Neurons: basic structure - Neurons: three major types - Glial cells: five major types - Internal cell structure - Protein synthesis - Protein packaging and shipment

Physical basis of electrical charge

- The world consists of matter - Matter consists of molecules -> water (H2O) - Molecules consist of elements -> hydrogen (H), oxygen (O) - Atoms are the smallest particle of an element that has the properties of that element - Atoms consist of: Protons (+) and neutrons (0) -> inside the center (nucleus) of the atom Electrons (-) outside the nucleus (orbit in electron shells) -> are involved in the electrical charge so they determine the charge of the atom - Ions are atoms that: 1) Have a surplus of electrons (anions, negative ions e.g. CI-) 2) or have a shortage of electrons (cations, positively charged ions e.g. Na+)

The action potential

- Unlike the regraded potential, the action potential is actually very brief, it's an all or nothing response; once it's initiated, there's no way back - A brief (1 ms) and large all-or-nothing potential that reverses the membranes polarity - Arises when the potential difference over the membrane exceeds a certain level: -> firing threshold (- 50 mV) -> once the cell membrane is depolarized to this threshold, the action potential is indicated - Unlike graded potentials, action potentials do not extinguish with distance and cannot be summed like gradual potentials -> a neuron needs to wait (=refractory period) until the action potential is over before it can generate another action potential (max. frequency ~200 Hz, sometimes ~1000 Hz)

Maintaining the resting potential

1. Potassium ions are allowed to passively traverse the inter and outer cellular fluid (K+) - Necessary to balance off the negatively charged large protein molecules; Channels allow K+ influx and efflux (passive transport) to balance intracellular A - 2. Gates usually prevent Sodium to traverse a cell membrane; That's why the concentration of Sodium is in general higher on the outside of the cell than on the inside; Gates prevent influx of Na+ 3. There are pumps, e.g. a Sodium - Potassium pump who allow some ions to pass the cell membrane and some ions not; In case of the Sodium - Potassium pump, it pumps Sodium out of the cell and Potassium into the cell in a ratio of 3:2; That's why there are always more Sodium ions on the outside of the cell than on the inside, which supports the resting potential, which is slightly negatively charged; Na+/K+ pump pumps Na+ out of the cell and K+ into the cell (3:2) costs energy! Both the gates and the pumps actually cost energy and only the channels are a process of passive transport

Firing threshold

= threshold potential. - At this threshold, the configuration of voltage-sensitive channels changes: They open briefly, enabling the ions to pass through.

Two types of refractory periods

Absolutely refractory period: depolarization + repolarization - It is absolutely impossible for the cell to fire -> This is the main cause why an action potential cannot be fired continuously, but only 200 times per second -> Not able to generate an action potential Relatively refractory period: hyperpolarization - The cell may fire, but it is more difficult -> Able to generate an action potential but it's more difficult

Action potential = reversal in an axon's membrane's polarity.

Action potentials are brief => many can occur within a second.

Resting potential

All nerve cells have a resting potential - they have the potential to generate (release) electrical energy -> The difference in electric charge between the inside and outside of a neuron's cell membrane (intracellular and extracellular side) ~ -70 mV = resting potential (potential energy) Ions critical to maintain resting potential: Cations Na+ Sodium K+ Potassium Anions Cl- Chloride A- Large protein molecules Intracellular more A- and K+ Extracellular more Cl- and Na+ - The way this works is that the negatively charged protein molecules actually have a higher concentration inside the cell and they are not allowed to traverse a cell membrane. - Potassium ions also have a larger concentration inside relative to outside the cell - Sodium ions, which are positively charged, are more concentrated outside the axon have a higher concentration on the outside of the cell, just as chloride So the main ions that are actually responsible for neurotransmission or transmitting of neuron information are Potassium (K+) and Sodium (Na+) -> This is because the large protein molecules can't traverse the cell membrane; and it's because of these large protein molecules that the default, so the baseline potential of the nerve cell is about - 70 mV

Two types of current

Alternating current (AC) -> home appliances with motors (e.g. vacuum cleaner) - In AC, the direction of current changes frequently (Socket: 50/60 Hz) - Advantage: more efficient transport and easier to change voltage (using transformers) - Disadvantage: human body is more sensitive to AC Direct current (DC) -> nervous system, batteries, (brain as a collection of many batteries) - In DC, the positive and negative terminals are always positive and negative.

The action potential; Closer look

At resting state, voltage sensitive Na+ gates are closed (-70 mV), When the firing threshold of -50mV is reached: 1. Voltage sensitive Sodium (Na+) channel briefly open -> Sodium rushes into the cell, which depolarizes the cell ; so it becomes more positive -> Na+ influx: difference becomes positive (+30 mV - above the baseline) -> depolarization 2. Once this limit (+30mV) is reached, the voltage sensitive Potassium gates open -> This allows for Potassium to rush out of the cell; Voltage sensitive K+ gates open -> K+ efflux: difference increases to resting potential (-70 mV) -> the cell becomes less positive -> repolarization (starts to depolarize until it is back at the resting potential) 3. The gates actually remain opened for just a couple of milliseconds after that; K+ gates still open -> difference increases beyond resting potential (-73 mV) -> hyperpolarization; because the gates are still opened, it sort of overshoots and becomes slightly more negative than the resting potential 4. The potassium gates close; K+ gates close: and the difference decreases to (-70 mV) -> resting potential Voltage sensitive sodium channels are more sensitive than potassium channels and open first Sodium channels have 2 gates -> Gate 1 opens at -50 mV treshold, Gate 2 closes at +30mV Potassium channels only have one gate -> opens at -50 mV but is less sensitive so small delay between Na+ and K+ opening of voltage sensitive channels

Electrical stimulation

Besides measuring voltage and current, one can also administer it -> that's basically how the brain cells interact Once you have administered it, you can also measure the potential difference

excitatory postsynaptic potential (EPSP)

Brief depolarization of a neuron membrane in response to stimulation, making the neuron more likely to produce an action potential

inhibitory postsynaptic potential (IPSP)

Brief hyperpolarization of a neuron membrane in response to stimulation, making the neuron less likely to produce an action potential

Maintaining the resting potential;2

Cell membrane = relatively impermeable to large proteins that are synthesized inside the cell (A- = anions) their negative charge is sufficient to produce a transmembrane charge (i.e. the resting potential) To balance the negative charge in the intracellular fluid produced by the large protein anions (A-), open channels allow potassium (K+) ions to cross the cell membrane. The potassium influx is limited by the concentration gradient across the cell membrane -> result is (slightly) negative charge across the cell membrane = resting potential -70 mV However, sodium can leak into the cell and may neutralize the resting potential (i.e. make intracellular fluid less negative) => sodium-potassium pump prevents this. sodium-potassium pump when a sodium ion leaks into the neuron, it is immediately excorted out by the sodium-potassium pump. 3 intracellular sodium ions are always exchanged for 2 potassium ions -> this ensures that the number of sodium ions is always larger in the extracellular fluid then inside -> which in turn contributes to the negative resting potential. (outside is always slightly more positive then inside of the cell) In sum: The cell's membrane channels, gates and pumps maintain the resting potential

Concentration gradient & Voltage gradient

Concentration gradient = difference in concentration of a particular molecule (numbers) between 2 areas (e.g. intracellular vs extracellular) Concentration gradient is basically diffusion but separated by e.g. a cell membrane 1) Impremeable membrane 2) Semipermeable membrane

Current

Current = an electrical charge that moves -> Unit of measurement = Ampère (A) Connecting two objects (or two poles within the same object) with different electrical charges (e.g. battery): -> charge moves from an area with a high concentration (surplus) of electrons (thus negatively charged) to a low concentration of electrons -> electrons flow from - to + = electron current (e.g. from amber - to wool +)

Dendrites collect information as graded potentials and the initial segment initiates discrete action potentials delivered to other target cells via the axon

Dendrites collect information as graded potentials and the initial segment initiates discrete action potentials delivered to other target cells via the axon. Hyperpolarization and depolarization can take place on the cell body membrane and on neuronal dendrites because these areas contain gated channels that can open and close, changing the membrane potential. Initial segment = area near of overlapping with axon hillock where the action potential begins. Unlike the cell body membrane, the axon is rich in voltage sensitive channels, beginning at the initial segment => channels open at particular membrane voltage Sometimes, action potential goes from initial segment into dendritic field = back propagation (this may make the dendritic field refractory to incoming inputs, reinforce signals coming into certain dendrites ...)

Impremeable membrane

Equilibrium for impermeable membrane = equal number of ions everywhere (c.f. diffusion of salt in water) Equilibrium -> concentration gradient You end up with one half where the salt is actually diffused in the water and the other half doesn't contain any salt Result -> Difference in charge across membrane Applying to the nervous system -> you can have a difference in charge between the intracellular and extracellular fluid just because there's a difference concentration of ions inside vs outside of the cell

electroencephalogram (EEG)

Graph of electrical activity from the brain, which is mainly composed of graded potentials from many neurons

Electricity

Greek: electron (ηλεκτρον) = amber (fossilized tree resin) -> If you rub amber with wool: electrical charge (static) Electricity is a natural phenomenon - Some fish are capable of generating electricity (e.g. eels) - Lightning (discharge of a potential difference in the atmosphere) - Human nervous system uses electrical signals to communicate -> type of electricity that we use in our brains is not the same type of electricity that fuels our smrtphone

The nerve impuls * nie ma tego slajdu na lecture

How does the action potential propagate along the axon? Two ways: 1) Continuous conduction - potential difference in one place activates nearby gates: domino effect video (1 minute) 2) Saltatory conduction - Axons are often wrapped in myelin = isolating layer (Schwann cells or oligodendroglia, see also Chapter 3) -> There are small 'gaps' in this isolation -> nodes of Ranvier -> The action potential can 'jump' from node to node video (3 minutes) NB: Saltatory conduction is faster and costs less energy than normal propagation Multiple Sclerosis: degradation of the myelin sheath in the CNS (oligodendroglia degeneration)

Magnitude of potential differences

If you measure nervous activity at the level of the skull you measure those signals at the level of microvolts because the nervous activity has to travel through the skull and then you loose some amplitude of the signal NB: Voltage range of neurons = 0-200 mV

Nerve impulses and behavior

In all our sensory systems, the conduction of information begins at ion channels. They initiate the chain of events that produce a nerve impulse. E.g. if you were to stroke your hand with a feather, the sensory neurons pick up these signals and start to convey the messages towards the interneurons which in turn innervate motor neurons, which make your hand move away

Voltage and current in the human body

In the nervous system, the current is not provided by a flow of negative electrons, but by a flow of (mostly positive) ions -> ions flow from + to - = ion current Main ions that are responsible for nervous activity: Na+ (sodium ion) K+ (potassium ion) Cl- (chloride ion) Ca2+ (calcium ion) NB: ions do not carry the same kind of electrical current that powers your phone Ions (the substances that are responsible for brain activity) -> max ~90 m/s (324 km/h) Electrons -> 270.000 km/s (90% speed of light) ~3 million times slower NB: ion current flows ~3 million times slower then electrical current Calcium ions play an important role in the release of neurotransmitters (= topic of chapter 5)

stretch-activated channel

Ion channel on a tactile sensory neuron that activates in response to stretching of the membrane, initiating a nerve impulse

For semipermeable membrane that only lets Cl- pass the membrane (Na+ remains on the left, or intracellular side):

Ions will move from an area of higher concentration to an area of lower concentration down their concentration gradient. -> you'll end up with something that is a mixture of a concentration gradient and a voltage gradient Some chloride ions will diffuse from the side of high concentration (left) to low concentration (right) However, some chloride ions will be 'pulled back' through the membrane because of the voltage gradient . Voltage gradient: difference in voltage between 2 locations (in this case difference in charge between negative chloride and positive sodium ions) Negative ions will move from an area of lower charge to an area of higher charge. Positive ions will move from an area of higher charge to an area of lower charge. Equilibrium for semipermeable membranes = Concentration gradient = Voltage gradient Left side = positively charged Right side = negatively charged -> the way this works is that some ions can actually traverse the cell membrane through gates, pumps etc., and then you get a difference in charge, not only because of the concentration gradient but also because of the voltage gradient who pulls some of those ions back into the cell Result -> Difference in charge across membrane largest difference close to membrane -> Because the gates are closed to the cell membrane, the difference in charge is actually the largest at this point

Motor neuron

Motor neurons send nerve impulses to synapses on muscle cells. The axon terminals contact specialized areas of the muscle membrane called end plates. On these muscle's end plates, the axon terminals release a neurotransmitter -> acetylcholine. Acetylcholine does not enter the muscle but attaches to transmitter-sensitive channels, which open when a neurotransmitter attaches at the receptor site. This in turn induces an influx of Na+ and efflux of K+ that may induce an action potential. NB: end plate channels are much larger than channels on axons and dendrites: allow both influx of Na+ and efflux of K+

Wave of infomration

Neurons can convey information as a wave, induced by stimulation on the cell body, traveling down the axon to its terminal. A voltmeter detects the waves's passage

How do neurons communicate

Neurons communicate through synapses (next lecture, Chapter 5) Cell A = presynaptic Cell B = postsynaptic In between the cells, this space (synaptic space) there are neurotransmitters -> Lets say that Cell A innervates cell b An action potential generated by presyaptic Cell A may cause graded potentials at postsynaptic cell B An action potential generated by Cell A can cause: 1) Excitation of cell B (= turn on) => excitatory postsynaptic potential (EPSP) may depolarize cell B (bring it closer to firing threshold) 2) Inhibition of cell B (= turn off) => inhibitory postsynaptic potential (IPSP) may hyperpolarize cell B (bring it further away from firing threshold) -> if one cell inhibits the other, it prevents it from actually creating an action potential

'tribo-' comes from the Greek word τρίβω (τριβή: friction, rubbing)

Other examples - running a plastic comb through your hair - rubbing a balloon against your hair - rubbing a plastic pen on a sleeve of clothes made of cotton, wool or polyester Because both the amber and wool are now electrically charged (either negatively or positively), any contact with an uncharged conductive object or with an object having substantially different charge may cause an electrical discharge of the built-up static electricity, resulting in a spark. NB: Lightning is the result of triboelectric charging of ice and water droplets within clouds

Na+ Sodium (cation) K+ Potassium (cation) Cl- Chloride (anion) A- Large protein molecules (anion)

Recall from slide 6 negatively charged ions (anions) have a surplus of electrons -> e.g. Cl- positively charged ions (cations) have a shortage of electrons -> e.g. Na+ NB: sodium and potassium most 'actively' involved in neural communication A- Large protein molecules manufactured inside the cell cannot cross the membrane -> their negative charge is sufficient to produce transmembrane charge (i.e. resting potential) Cl- does not add much: point at which concentration gradient = voltage gradient ~ resting potential

Electrical charge - potential difference (voltage)

Rubbing wool against amber causes negatively charged electrons to "jump" from the wool to the amber (triboelectric effect) - The amber gets a surplus of electrons (becomes negatively charged because electrons carry a negative charge) - The wool gets a shortage of electrons (becomes positively charged) There is now a difference in charge between the wool and the amber - This is called a potential difference or voltage - Unit voltage: Volt - Measuring voltage: Voltmeter NB: it is a relative difference -> 2 connections needed to measure (e.g. 2 poles on a battery) -> just like in batteries you can actually measure the difference in charge between any two objects

Sensory neuron

Sensory neurons transmit neural information from sensory receptors to spinal cord and brain. The base of each hair on our body is wrapped in a dendrite of a touch neuron. Displacement of the hair opens stretch-sensitive channels in the dendrite's membrane which results in an influx of sodium ions (Na+). This in turn causes voltage-sensitive sodium and potassium channels to open, producing an action potential.

Summation

The location of where the EPSP and IPSP occurs also determines whether the cell actually fires; whether it generates an action potential or not The net effect of all EPSP's and IPSP's determines whether a cell fires NB: If the potential difference at the initial segment on the axon hillock becomes smaller than the -50 mV threshold, an action potential is propagated along the axon -> the cell 'fires' In general: graded potentials that occur near or more closely to the axon hillock (where the axon starts) have more influence on the ability of the cell to fire; -> So even if you have enough e.g. EPSPs at the beginning of the cell, an inhibitory potential can actually prevent those EPSPs from firing the cell Graded potentials typically occur on the dendrites and cell body Action potential occurs at voltage-sensitive channels, near the axon hillock -> There are also voltage-sensitive channels on the dendrites and cell body, but they're more numerous at the axon part of the cell NB: in some neurons also on dendrites -> back propagation

50 Hz AC is much more fatal then a 2000 or 4000 Hz or 5 Hz AC of the same magnitude.

The reason being, at 50 and 60 Hz, the electrical pulses from the shock stimulate the body's muscles and interfere with our own nervous system.

How do nerve cells interact with each other; generally; SUMMARY

There's always some flow of ions that generates or inhibits a type of behavior

Graded potentials - Stimulating a neuron

Two options: Apply a negative charge (voltage) - hyperpolarization (inside of a cell becomes even more negatively charged) -> K+ efflux or Cl- influx; both actually result in the intracellular fluid becoming more negatively charged - potential difference increases from -70 mV to -73 mV (gradual change) Apply positive charge (voltage) - depolarization (becoming less negative or more positive and it's actually moving towards the baseline of zero mV)-> Na+ influx - potential difference decreases from -70 mV to -65 mV (small difference again) NB: both options induce graded potentials -> small fluctuations across the cell membrane that extinguish with distance and can be summed Hyperpolarization and depolarization can take place on the cell body membrane and on neuronal dendrites because these areas contain gated channels that can open and close, changing the membrane potential.

Resting transmembrane charge

Unequal distribution of different ions causes the inside of the axon to be relatively negatively charged

How do neurons communicate?

Unlike the action potential, graded potentials (EPSPs and IPSPs) can actually be summed and the way they are summed is both in temporal location so once they are initiated at the same time, they may be added and form a larger EPSP or IPSP and they can also be summed if they occur at locations close together, so there's spatial summation and temporal summation of graded potentials -> For instance if you have an EPSP and an IPSP occurring at the same time in same location, they may be able to cancel each other out

Effects of current on a human body -> Background knowledge, not for the exam

Values for AC (multiply by ~4 for DC) In general, everything up until 10 mln ampers is maybe painful but is not harmful Current strength also depends on resistance -> Current = Voltage / Resistance (Ohm's law: V = I*R; I = V/R) Legally: AC voltage max. 50 V, R ~ 5000 Ω → I ~ 10 mA In the human body, the skin has the most resistance (about 100,000 ohms), while the internal organs, muscles and tissues have a resistance of about 300-500 ohms.

Diffusion (basically what happens if you diffuse Salt (NaCl) in Water (H2O)

Water = H2O -> hydrogen H+ (positive) + hydroxide OH- (negative) Salt = Na+ Cl- (sodium chloride) Diffusion (passive process) -> Na+ binds with negative poles (O) -> Cl- binds with positive poles (H) Equilibrium = equal number of molecules everywhere In diffusion, ions passively move (without use of energy) from an area with a high concentration to an area with a low concentration. When diffusion is complete, a dynamic equilibrium, with an equal number of molecules everywhere is the result Example: dissolving salt in water -> That's the most basic passive process of transferring ions and thus generating electricity

microelectrode

a microscopic insulated wire or a saltwater-filled glass tube whose uninsulated tip is used to stimulator record from neurons

spatial summation

addition of one graded potential to another that occur close in space

temporal summation

addition of one graded potential to another that occur close in time

initial segment

area near where the axon meets the cell body that is rich in voltage-gated channels, which generate the action potential

depolarization

decrease in electrical charge across a membrane, usually due to the inward flow of sodium ions

volmeter

device that measures the strength of electrical voltage by recording the difference in electrical potential between two points

concentration gradient

difference in the relative abundance of a substance among regions of a container; allows the substance to diffuse from an area of higher concentration to an area of lower concentration

resting potential

electrical charge across the insulating cell membrane in the absence of stimulation; a store of potential energy produced by a greater negative charge on the intracellular side relative to the extracellular side; Channels, gates, and pumps in the cell membrane contribute to the transmembrane charge

voltage-activated channel

gated protein channel that opens or closes only at specific membrane voltages

Spatial summation

graded potentials that occur close in space are added

Temporal summation

graded potentials that occur in quick succession are added

hyperpolarization

increase in electrical charge across a membrane, usually due to the inward flow of chloride or sodium ions or the outward flow of potassium ions

action potential

large, brief reversal in the polarity of an axon membrane

back propagation

reverse movement of an action potential into the soma and dendrites field of a neuron; postulated to play a role in plastic changes that underlie learning (plasticity)

graded potential

small voltage fluctuation across the cell membrane

oscilloscope

specialized device that serves as a sensitive voltmeter, registering changes in voltage over time

absolutely refractory

the state of an axon in the depolarizing period, during which a new action potential cannot be elicited (with some exceptions) because gate 2 of sodium channels, which are not voltage activated, are closed

relatively refractory

the state of an axon in the later phase of an action potential, during which higher-intensity electrical current is required to produce another action potential; (it's more difficult); a phase during which potassium channels are still open

threshold potential

voltage on a neural membrane at which an action potential is triggered by the opening of sodium and potassium voltage-activated channels; about -50mV relative to extracellular surround. Also called threshold limit