Electrical Signals/Properties of Nerve Cells Flashcards
How does transmission of information occur in the cells?
Transmission of information happens through the movement of ions (charge) across the plasma membrane in response to the opening of ion channels (ions cannot just cross the membrane without specific channels that allow them to cross). The movement of these ions across the membrane can be measured as electrical impulses (current).
At the beginning, you have these small graded changes in the membrane voltage and these end up being summated or not summated into all or none action potentials.
The intracellular and extracellular spaces at rest
At rest, the inside of the cell is more negative than the outside of the cell. This makes the charges want to cross the ion channel to creat an equilibrium. This is the potential energy stored in charges that want to cross.
* Intracellular: -65mV
* Extracellular: 0mV
Receptor and Synaptic Potentials vs Action Potentials
Receptor and Synaptic Potentials are graded. These potentials will not reach back to the nervous system on its own. They are transcient.
* Receptor potential = potential due to any receptor on a neuron.
* *Synaptic potential *= occurs at sunapse (most will be synaptic).
Action Potentials are all-or-none and regenerative. They are massive, fast signals. They are short in duration but can travel long distances. They are self-sustaining.
Passive vs Active responses
Passive: no activity is going into the system to allow it to propagate, so passive potentials slowly die away on their own. Don’t require input of energy from the cell.
Active: Some action is being taken to allow for the potential to propogate, allowing it to keep a constant size as it moves. Require input of energy from the cell.
Differences between receptor potentials and action potentials
Receptor Potentials (EPSPs/IPSPs):
-graded
-passive
Action Potentials:
-all or none
-active
-regenerative
Passive responses can summae into active responses.
Why does the cell have a negative resting potential?
The normal negative resting potential is a way for neurons to store the energy used for rapid signaling (PE).
Synaptic potentials
all synaptic potentials are receptor potentials, but not all receptor potentials are synaptic potentials. (Synaptic potentials = sum of all local potententials.
What is the importance of the input and output?
Graded inputs summate to action potentials.
* Importance of input = amplitude of IPSP/EPSP
* Importance of output = frenquency of AP
Amplitude of input determines frequency of output.
Action potential size doesn’t vary like current size does, just the frequency. The frequency is a proxy of how strong the input is.
Temporal Summation
Two inputs come in at the same spine close together get summated very quickly. Whereas if there were two inputs that come in far apart they might not even get summated at all because the signal has already left.
**Time and space are important variables for whether 2 signals get summated. **
What happens if an EPSP or IPSP does not end up firing an action potential?
If something happens (EPSP or IPSP), and the cell doesn’t end up firing an action potential, then that cell will not trigger EPSPs/IPSPs in the next cell and the “message” encoded by the action potential will be lost. The signal that created the first EPSP/IPSP dies.
How do neurons communicate?
Action potentials are the language that neurons communicate with.
Information is conducted throughout the nervous system using electrical impulses:
* Ions=charge (positive or negative)
* Charge movement across membranes = current (can also be + or -). Depends on direction of motion or the sign of a charge:
-Negative charge leaving cell = net +
-Positive charge entering cell = net +
-Positive charge leaving the cell = net -
-Negative charge entering the cell = -
Inside the cell is ____ charged and outside the cell is ____.
Inside the cell is negatively charged compared to the outside of the cell.
What do inputs do?
Inputs (opening of ion channels on a cell membrane) induce graded changes in membrane voltage (EPSP or IPSP).
* These inputs get summated to create the output which is action potentials.
* All the electrical inputs on a cell sum up to either trigger or not trigger an anction potential (“all or none”) aka spikes.
What does depolarize mean?
Membrane potential is getting more positive
What does hyperpolarize mean?
membrane potential is getting more negative
Explain the concept of current and voltage in the cell
The flow of current across the membrane causes a change in membrane potential (aka voltage).
When you are recording the “voltage of the cell”, you’re measuring the difference in charges on the inside vs outside of the cell, we also call this membrane potential.
Resting membrane potential
Voltage difference between inside and outside of a resting neuron (around -65mV to -80mV).
Action Potential threshold
Threshold for firing an action potential that EPSPs need to sum in order for the cell to fire (around -40mV).
Once a healthy neuron’s membrane potential becomes more positive than the AP threshold, it will always fire an AP.
Excitatory Postsynaptic Potential
Small excitatory event that makes the membrane depolarize
Inhibitory Postsynaptic Potential
Small inhibitory event that hyperpolarizes the membrane and makes it harder to reach AP threshold.
Ions in solution
Ions in solution are surrounded by a hydration shell.
* Ions in solution are surrounded by polar H20 molecules -> big profile.
* Can’t pass the plasma membrane/ lipid membrane because it is hydrophobic. The plasma membrane offers a resistance to the ionic flux.
* Need these specific transporters and channels (conductance) to remove hydration shell and allow passage of ion.
* Ion channels can selectively strip off the shell. Channels are selective: not all channels conduct all ions.
Conductance
Conductance is a measure of permeability to ionic flux.
Transporters and Channels
Transporters and channels permit ions to cross the hydrophobic plasma membrane.
Ions Transporters
- Actively move ions against concentration gradient
- Create ion concentration gradients: high internal [K]; low internal [Na].
Ion Channels
- Allow ions to diffuse down concentration gradient.
- Cause selective permeability to certain ions
Ex: when Potassium exits the cell, it is leaving other negatively charged species that were associated with it and cannot cross membrane.
Leak Channels
Leak channels are open all the time.
* They are selective.
* Potassium freely diffuses out because there is so much more inside.
Why don’t all the ions transported into the cell just exit via channels?
Channel selectivity and electrostatic force
Chemical Diffusion
Chemical diffusion is balanced by electrostatic forces at equilibrium.
As potassium moves from the inside compartment to the outside, a potential is generated that tends to impede further flow of K. This impediment results from the movement of K to the outside compartement but the staying of - charges on the inside. Thus, as the outside becomes + relative to the inside, the increasing positivity makes the outside less attractive to the positively charged K (similar charges repel).
As K ions diffuse and encounter the membrane channels, more will pass from the side where K is higher, simply by chance. Consequently there is a net movement of K ions from high to the low concentration sides.
However, this now seperates the + charge of the K ion from the - charge of the Cl ion, creating an electrical potential difference between the two sides. Consequently, electrostatic force drives (+) K ions back toward the (-) charged side.
At equilibrium, the number of K ions diffusing down their concentration gradient equals the number drawn back due to the charge inbalance.
Walther Nerst
- Third law of thermodynamics (absolute zero)
- Nernst lamp (first electric light bulb)
- Neo-Bechstein-Flugeil electric potential
- Chemical Warfare (coat bullets in chemicals)
- Nerst equation
Nerst Equation
- Determined in 1888 from basic thermodynamic principles.
- Restates concentration gradient in electrical terms
- used to calculate the equilibrium/reversal potential.
- Temperature MUST be in KELVIN - take celcius value and add 273.15.
- Z will be -, if it is a negative ion
E is called the equilibrium potential (voltage at which the system has reached equilibrium).
- E = membrane voltage (Vm) at which there is no net movement of ions. It is the most energetically favored membrane voltage.
How much do you have to change the [K] out to get a 58 mV increase in Vm.
Increase extracellular [K] 10-fold
How much do you have to change [K] out to get a 58mV decrease in Vm
Decrease extracellular [K] to 1/10th
How much do you have to change [K]in to get a 58mV decrease in Vm?
Increase intracellular [K] 10-fold
What is the formula for Ek
What happens when you apply a voltage across the membrane?
Applying a voltage across the membrane will also modify its ionic flux.
* When the battery is turned off. K+ ions (gold) flow simply according to their concentration gradient. Setting the initial membrane potential (Vin-out) at the equilibrium potential for K+ yields no net flux of K+.
* Wherease making the membrane potential more negative than the K+ equilibrium potential causes K+ to flow against its concentration gradient.
The graph demonstrates the relationship between membrane potential and direction of K+ flux.
Several different ion channels (mainly K, Na and Cl) contribute to the resting potential of a neuron. Do they contribute equally?
No, they do not contribute equally because of the different permeability at rest of those ions and the permeability is set by channels.
* K+ has a strong influence on Vm. Changing [K]o dramatically shifts Vm.
* Turns out that for a resting neuron, huge changes in [Na]o hardly impacts its Vm.
* The value of the resting membrane potential is a weighted balance of the reversal potential of K, Na and Cl.
In what direction does potassium and sodium flow in and out of a cell?
Because of the Na/K transporter:
* [K]i > [K]o (potassium is considered the intracellular ion)
* [Na]i < [Na]o (sodium is considerd the extracellular ion)
Standard: 25.7ln…
How do you calculate Vm for membranes permeable to multiple ions?
Goldman-Hogkin-Katz (GHK) equation: Weighted “average” of Nerst potentials for multiple ions using relative permeabilty as weighing factor.
Driving force
The potential energy that can be activated when a channel is opened.
* The driving force on an ion is greater the further Vm gets from that ion’s equilibrium potential.
What causes rapid depolarization during an action potential?
Rapid depolarization during an action potential is due to the sudden opening of many Na channels. Unlike at rest, changing [Na]o (extracellular) during an action potential greatly impacts membrane voltage.
Diagrams:
Graph A shows that if you modulate the concentration of potassium over time you will increase the resting membrane potential of the cell.
Graph B shows that the increase in the resting membrane potential of the cell is not linearly related to the concentration of potassium (exponentially related). Slope itself is 58mV. So if you increase the extracellular potassium by 10-fold you will get an 58mV increase.
Graph D if you increse the extracellular sodium then the action potential amplitude will increase. Will increase by 58 mV if you increase ectracellular sodium by 10-fold.
Graph E if you change the extracellular sodium it has no impact of resting membrane potential.
Resting and action potentials rely on what?
Resting and action potentials rely on permeabilities to different ions.
At rest, neuronal membranes are more permeable to K+ (gold) than to Na+ (red): accordingly, the resting membrane potential is negative and approaches the equilibrium potential for K+, Ek. During an action potential, thje membrane becomes very permeable to Na+ (red); thus, the membrane potential becomes positive and approaches the equilibrium potential for Na+, ENa. The rise in Na+ permeability is transient, however, so the membrane again becomes primarly permeable to K+, causing the potential to return to its negative resting value.
Synaptic events that produce an EPSP
Synaptic events that produce an IPSP
Electrochemical gradient
The electrochemical gradient dictates everything that happens in the cell. It is the balance of electrostatic forces and chemical forces.
One container with two compartements. The compartements are seperated by semi-permeable membrane that only allows potassium through. On each side, is potassium chloride (KCl) same concentration (1mM). There is no net flux because the potassium is already evened out chemically and no current is running (0 mV being applied).
BUT if you hade 10mM in chamber 1 and 1mM in chamber 2 with 0Mv being applied then you would have a net flux of potassium going from the 10mM chamber to the 1mM chamber to even out the concentrations through diffusion.
The electrochemical gradient is where lets say you applied -58mV difference between the two chambers then that concentration gradient would not result in flux from chamber 1 to chamber 2 because of the electrical balance from the -58mv. We would consider this electrically balanced. Where potassium doesnt need to flow from one chamber to the other to even things out because it is already evened out from the electrical point of view - so the concentration remains the same. This is what happens in a cell at rest when you have ions that are able to cross the membrane or not able to cross the membrane and that are present in varying concentrations based on the electrochemical gradient.
Matteuci
- Wanted to take Galvani’s experiment a steo further: if the musculature can produce electrical current itself, should be able to activate a second nerve/muscle, even without the battery.
- He took the nerve from one muscle (fascia) and then connected it to another muscle. He saw that the activation of first muscle generated current that went to second muscle and created a twich. So, “excitable tissue can both sense and produce electricity.)
Voltage Clamp set up
- Both of the electrodes are recording the specific voltage at their location:
-reference electrode is recording voltage outside of system. -recording electrode is recording voltage insise the system.
-there is a third electrode that allows you to inject current. - You are telling the system, what you want the membrane to be. Measures what the current membrane potential is and then it decides how much current it needs to inject in the background to keep the membrane at that potential. Mesures the membrane potential continouously.
- Membrane potential that is being recorded, is being held at a membrane pottential (does NOT change). All tthat can change is the current flowing into the membrane and that is being recorded. Voltage clamp = recording current because you are controlling voltage.
Voltage clamp recordings
- Hyperpolarization from -65mV to -130mV: doesn’t cause any additional channels to open, so no currents observed; however, membrane current wouldn’t necessarily be 0 because at more negative potentials, you increase driving force for all ions.
- If you depolarize the cell, you would have a transcient inward current and delayed outward current.
- Depolarizing the cell from the normal resising potential activates voltage-senstive ion channels, resulting in measuring currents.
What are the two primary identifying moments of an action potential?
As you depolarize Vm (go more positive):
* Transient Inward Current (Na+) increases (gets bigger), then reverses and goes back inward. With increasing voltage steps, it gets bigger, then smaller and eventually reverses direction above +52mV.
ENa = +52 mV
Driving force for Na = Vm - ENa
(Less than 100% of voltage-gated Na channels are open at hyperpolarized potentials)
- Delayed Outward Current (K+): continues to increase. As you continue to depolarize, current keeps getting bigger because we are continuously getting further away from reversal potential of potassium.
How can we determine which ion species mediate the AP (method 1)?
Prepare an extracellular solution with no sodium. Eliminate underlying ion species, Na-free medium, early current is outwards instead of inward. However, if you restore back to original Na concentration, then current is large and inward again.
The early current is mediated by Na+
- early current reverses in low Na external but late current is unaffected.
How to determine which ions mediatate the Action Potential (method 2)?
Often used concept on short answer questions
Pharmacological blockers (drugs) -> sodium and potassium channel blockers. They block voltage-gated ion channels with toxins.
1) TTX
* Toxin from the liver and overies of puffer fish.
* Blocks voltage gated sodium channels.
* Look at late current/ K current only.
2) TEA
* K+ channel blocker
* look at early Na current.
* This method could also calculate conductance
Explain the steps of the action potential
At rest, you have a cell that is just at rest.
1) Stimulus: often there are multiple stimuli that don’t summate and are not big enough. One that is big enough hits threshold (-55mV) and the action potential is initiated.
2) Depolarization: huge influx of sodium channels during the depolarization that reaches a peak close to the reversal potential of sodium (approx +50ish).
3/4) Repolarization: Potassium flows out of the cell until you reach the trough of the of the AP, which there is hyperpolarization. Sodium chanels fly in.
5) Go back to resting state.
What is the calculation for the conductance of a given ion?
For any given ion (x), the conductance (gx) of this ion is equal to the current carried by that ion (Ix) divided by its driving force (Vm-Ex).
How does the sodium conductance, potassium conductance and overall current change during an action potential?
Properties of conductance during the action potential
- Na conductance is transient (rapidly inactivates) - it comes and goes.
- K conductance is delayed but doesn’t inactivate.
- Both plateau at positive membrane potentials once all the channels have opened.
Important to remember: conductance amplitude is double the size for potassium compared to sodium becasue there are more pottasium channels.
During an AP, there’s a very systematic change in conductance of membrane as a function of voltage: as you get more Na channels open, more k channels open and thus more current will flow, eventually plateau as you max out the # of receptors that can open. Similar for Na and K, but rememer differences in kinetics.
Feedback cycle
Feedback cycles are responsible for membrane potential changes during an action potential. Membrane depolarization rapidly activates a positive feedback cycle fueled by the voltage dependent activation of Na+ conductance. This phenomenon is followed by the slower activation of a negative feedback loop as depolarization activates a K+ conductance, which helps to repolarize the membrane potential and terminate the action potential.
What is the refractory period?
Period of time during which the membrane cannot regenerate a second full-sized AP due to the inactivation of Na channels.
1) Absolute refractory period: Second stimulus completely fails to produce AP. Try to fire another AP close to the first one (within 4.5 ms) and during this time all of the sodium channels are inactivated.
2) Relative refractory period: not a full blown AP but some Na channels still open so you get a partial AP. Not very effective and usually does not recelease neurotransmitter.
3) If you wait around 9ms then you can generate a whole new action potential.
How do Na channels function?
Na channels can either be open, inactivated or closed. Inactivation is between open and closed.
Sodium channels will open, close rapidly and become inactivated before going back to closed state at negative memrane potentials. Thus, 3 states (repeat states) is the basis of refractory period.
There is a subunit within the protein, within the body of the protein (one of the transmembrane domains) that is voltage sensitive. When the cell depolarizes it moves up wich causes a conformational change in the whole channel causing the pore to open.
How do K channels function?
K channels just open and close. They only open and close dependent upon membrane potential. They open much more slowly than Na channels.
*Keep in mind the diversity of Na and K channels.
Explain the Ball and Chain model of inactivation
- Intracellular Pronase removes inactivation.
- The longer the chain, the longer it takes to inactivate because the lower the chance of the ball entering the pore and the longer it takes to deinactivate.
- Entry of ball = stochastic (randomly)
- Exit of ball = hyperpolarization + stochastic
Remember: the ball and chain is not the same as the pore. The ball and chain comes from inside the channel when the pore is still open.
Open -> inactivated -> de-inactivate in order to close.
Do sodium and potassium have an end to their conductance?
- Sodium has an end to the conductance because it inactivates.
- Potassium does not have an end to conductance since it does not innactivate.
How does the refractory period allow for unidirectionality of information?
If you deopolarize and get an AP at one site, then charge would spread and activate adjacent regions of membrane on either side. At the next site, AP would be initiated but previous site wouldn’t generate an AP since its in refractory period and Na channels are still inactivated. Thus, AP can only propogate in one direction and also previously excited part of axon can now send more AP down it.
It is important to have refractory period (sodium channel inactivation) to maintain unidirectionality.
