Lecture 1 chapters 2&4 - electrical signals of the nerve cells
How do neurons communicate?
- They need electrical signaling in order to communicate
- Neurons limitations:
o Our cells are made out of lipids, so they do not conduct electricity very well. They are also poor
generators. This is the most important challenge that the neurons have
- In order to solve these limitations, the neurons make pores in order to pass the membrane
Neurons
- Make electrical signals that are based on the flow across the membrane
- 2 important aspects:
o Differences in concentrations of ions inside and outside the membrane
o There is selectivity on which ions can pass and at what time
Examples of electrical signals in brain/skin
- Electrode measures electrical signals = when putting this on your skin, you can record field potentials of any
receptors in your skin. You can record electrical currents = receptor potentials
- Synaptic potentials = taking an electrode --> putting it on the axon (the blue part on the axon) which is very
small --> measuring electrical current
o Synaptic potential happens upon activation of a single synapse
o Electrical current =
▪ It will trigger synaptic vesicle fusion
▪ Does not do much on the post synaptic neuron
- Action potential = when the threshold potential is reached then an action potential happens
o Occurring in all neurons
Recording electrical signals in brain neuron
- Research = 2 electrodes used --> 1 stimulating the neuron and 1 recording the membrane potential
(difference outside and inside)
o Inserting micro electrode
o Injecting electrical current in the membrane
- When measuring the response of neuron to the current (to stimulation) you see:
o When injecting little bit of negative current causes lower resting membrane potential =
hyperpolarize the membrane --> the more negative you inject, the more negative the resting
membrane potential becomes
▪ Stopping the injection of current = signal stops
o Positive current injection
▪ Injecting a little bit more current (increasing the strength of the electrical current) = action
potential occurs (when threshold is reached)
• Membrane potential goes from -60 to +40 mV
▪ When doubling the current = the height of the action potential does not increase but you
see that there are more action potentials happening. The strength of your stimulation is
encoded in the frequency of your action potential: stronger stimulation (higher current )=
more action potential
o This phenomenon cannot be suppressed
o Enough current is needed to pass the threshold
,How the brain communicates
- Neuron connected to one synapse
o When fusing with 1 synaptic vesicle they stimulate the neuron
o When there are more synaptic vesicles --> they together might reach the threshold
- Neurons transfer information via electrical signals
- At rest neurons have a negative resting membrane potential
o Negative current injection = hyperpolarization
o Positive current = depolarization
▪ If this is high enough, you reach threshold --> action potential
Purpose action potential
- Without action potentials you cannot live
- They carry information
o The higher the stimulation = the stronger the signal
- Action potential allow for long range signal transduction
o Stimulating at 1 place = local depolarization of membrane
o Membrane is made up of lipids and is very large = so the current dies off very fast. The stimulation
cannot move very long along the membrane.
o So = without action potential, the stimulation does not move very far
- Stimulation at 1 place but you give enough current to create an action potential
o This moves all the way along a very long synapse
o Intensity and amplitude does not change
Ion movements
- Every neuron at rest has a negative potential. Why:
o Plasma membrane is impermeable to ions
o Concentration differences of specific ions across the membrane
▪ Most important one for action potential regulation = K, Na, Cl, charged proteins
▪ A lot of potassium on inside
▪ A lot of sodium on outside
▪ This chemical gradient is kept this way due to the impermeability of the membrane
▪ There is a pump in your brain that uses 30% of your brain energy = sodium potassium pump
• Pumps ions against their gradient
• It is an active transporter
• Maintains the concentration gradient across the membrane
• 2 K ions in and 3 Na ions out
▪ Channels in membrane = protein pores
• Allow ions to flow through the lipid because they make a hole
• This hole can be closed and it is very specific to the different types of ions
• Allow ions from high concentration to low concentration
• The opening and closing is depending on the membrane potential
Diffusion and electrical forces at rest
1. K+ - channels open = the potassium leaks from high concentration to low concentration --> negative
potential inside
o Na+ channels closed
2. Electrical force pulls positive K+ ion back to the cell
- Electrochemical equilibrium
o No net flus of K+ seen because outside and inside concentration of K+ is the same
o A lot of K + on inside and less on outside causes net flux of K+ from inside to outside
▪ Flux of K+ from inside to outside balanced by opposing membrane potential
, o Ex = equilibrium potential for any ion
▪ For the simplified formula you only need the
• Valence of the ion
• And the concentration differences
▪ For potassium you get -58 mV
• Most neurons have the resting membrane
potential of -58. So this is actually mostly
regulated by the potassium concentration
▪ For sodium you get +58
o Goldman equation = for all ions at the same time
▪ (figure 2.7) Ion basis of action potentials
• Resting potential = the permeability for potassium is higher than for sodium
• Action potential caused by the sudden opening of sodium channels
• After the action potential is caused repolarization happens
Squid giant axon
- They have giant axons because they squirt water to their enemies
- The bigger the diameter = the faster the potential through the axon
(Nerve bundle = a bundle of nerves)
Voltage clamp technique to simultaneously control and measure membrane potential
- Putting in electrodes =
o Green = records current
o Battery that injects current through the yellow axon
- Using this, the researchers could clamp at a certain voltage
- What they found out in squid axon:
o Resting membrane potential = +65 mV
- When action potential is induced =
o Inward fast and short-lived current = sodium
o Outward slow and lasting current = potassium
- Experiment
o Washing away all the sodium or blocking all the sodium channel =
▪ Blocking by using tetrodotoxin which is a toxin from the puffer fish (no known antidote)
▪ Results =
• The inward current was lost and the inward current was still there
o Removing potassium = outward current was gone
- Concluded
o If I give a current to an axon that passes the threshold, we get an inward current due to the sodium
o The outward current is then caused by
potassium = the delayed efflux
The patch clamp method
- Pushing against the membrane of an axon by a
micropipette
- You capture a few ion channels
- You can inject current and measure the flow of ions through these few ion channels at the same time
- Results
o 15 pA = approximately 10 million sodium ions per second
o 15 pA is 1 trillionth the current in household outlets
, ▪ These microscopic NA currents add up to macroscopic AP
o The currents that they measure are very small
o Adding up all the small currents generates an action potential
What happens during action potential?
- Resting membrane potential: Permeability gK > gNa
- Steps (1-6) =
1. Open K+ channels create the resting potential
2. Any depolarizing force will bring the membrane potential closer to threshold
3. At threshold, voltage-gated Na+ channels open up, causing a rapid change of polarity (the action
potential)
4. Na+ channels are inactivated; gated K+ open up, repolarizing and even hyperpolarizing the cell
(afterpotential)
5. All gated channels close. The cell returns to its resting potential
6. After polarization is important because during this time the membrane is refractory = when the
membrane is hyperpolarized, you cannot trigger an action potential
Aps are generated at the axon hillock
- Axon hillock is in between the neuron and the axon
- Once they are polarized (get an axons), they have to maintain this axon for their whole life
o Checkpoint that only allows axonal proteins and removes the dendritic axon
o When it gets dendritic axons = it starts to generate a spine --> becoming a dendrite
o Ankyrin protein = very impotant!!
o Nodes of Ranvier also contain these ankyrin proteins so that the action potential is sped up
- So the function of axon hillock
o Maintenance polarity of neuron
o Creating action potential
- PSD93 = post synaptic density protein 93
o Causes clustering of more potassium channels and sodium channels
o It prevents invasion of dendritic proteins into the axon
- Caspase is enzyme in your brain
o If the cell membrane of neurons are disrupted. Massive influx of Ca2+ --> caspase cleaves the
ankyrin --> axon terminized
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