The Single Neuron & Electrophysiology Flashcards
What are the four functional regions of the neuron? Name the structure corresponding to these regions in a typical neuron.
Most neurons, regardless of type, have four functional regions in which different types of signals are generated.
- *Input**: dendrites;
- *integration**: soma/axon hillock;
- *conductive**: axon;
- *output**: synapses/axon terminals
Where in the neuron is an action potential initiated? Why?
Action potentials or spikes are initiated at the axon initial segment (AIS), or axon hillock, which is also called a trigger zone. There is a large concentration of Sodium Channels at the axon initial segment.
What is a synapse?
A synapse is a specialized structure allowing communication between neurons.
It commonly appears between the axon of a pre-synaptic neuron and the dendrite of the posts-synaptic neuron (but there exist ‘dendro-dendritic’ and ‘axo-axonic’ synapses as well).
In general, as the intensity of an input stimulus increases, the ______ of the action potentials increases as well.
firing rate / spike rate / firing frequency
Neurons can encode the stimulus strength as a spike rate. This kind of coding scheme is known as rate-coding.
What is the membrane potential (Vm)?
The potential that results from a separation of charge across the cell membrane (voltage). In other words, it is the difference in electric potential between the interior and the exterior of a biological cell.
What makes a neuron an “excitable cell”?
The presence of voltage-gated ion channels makes a neuron an excitable cell.
The term excitable refers to the ability of some cells to be electrically excited resulting in the generation of action potentials. Neurons, muscle cells (skeletal, cardiac, and smooth), and some endocrine cells (e.g., insulin-releasing pancreatic β cells) are excitable cells.
https://www.physiologyweb.com/glossary/e/excitable_cell.html
What is the Nernst equation and what does it calculate?
With the Nernst equation you can calculate the equilibrium potential for a given ion.
Remember that the [square brackets] represent concentration and R, T, z and F are all constants; T is the absolute temperature; z is the valency of the ion.
How can we calculate the membrane potential (Vm) of cells if we know 1) the concentration of ions inside and outside the cell, 2) the conductances in the membrane?
When more than one ion channel is present in the membrane, the membrane potential can be calculated by using the Goldman-Hodgkin-Katz equation (GHK equation). Usually, only K+, Na+, and Cl- are implemented;
* The larger the P (permeability), the more it contributes to the membrane potential.
Which two fundamental physical forces are at play in establishing the equilibrium/Nernst potential ($V_eq$) of an ion?
The equilibrium/Nernst potential (Veq) is the voltage at the point where the chemical gradient (as a result of ion type distribution) and the electrical gradient (+/-) cancel each other out and are thus, in balance.
What is an ion?
Ions are atoms with a charge. There are cations (positively charged ions +, such as Na+, K+, and Ca++) and anions (negatively charged ions -, such as Cl-).
The charge of the ion is its valence.
The membrane potential (Vm) is a function of the electrochemical gradient. What are the two competing forces in the electrochemical gradient?
- The asymmetric distribution of ions across the plasma membrane (ion concentration gradients)
- The selective permeability of different ions by the plasma membrane (ion channels).
What is the value of the resting membrane potential (Vrest) in a typical neuron?
The value of the resting membrane potential varies from cell to cell, from about −20 mV to −100 mV.
A typical Vrest is often around -70mV
What is the main difference between passive ion channels and active ion channels?
Passive channels, also called leaky channels have constant permeability, irrespectively of voltage.
An active channel is a channel that can open or close in response to changes in the environment. Voltage-gated channels open and close in response to changes in membrane potential. Ligand-gated channels open and close in response to the presence of a molecule (ligand).
Looking at the Nernst equation, which factors have a significant impact in determining the Equilibrium potential?
(1) the concentration gradients [X]e/[X]i
(2) the valence (z) of the ionic species in question
(3) temperature.
Describe each stage of an action potential in the image
- The neuron at its resting membrane potential.
- Depolarisation. Results from Na+ channels being opened, causing an influx of the positively charged Na+ ions. This leads to the inside of the cell becoming more and more positive (relative to the outside).
- Overshoot. Here, the membrane potential becomes positive.
- Peak. At this point, pNa is 600x greater than at its resting value.
Vm is close to VNa, though never reaches it because…
- The Voltage-gated Na+ channels begin to inactivate rapidly after they open.
- Neurons have Voltage-gated K+ channels that become activated by membrane depolarisation as well, but they open much slower. This is why these channels are called delayed rectifiers. Similar to the permeability of sodium, at the peak, the PK is (about three times) greater than at rest.
- Repolarisation. The outflux of K+ causes the inside of the cell to become more negative again, taking the neuron back to its resting value.
- Hyperpolarisation. When the resting potential is reached, the K+ channels do not immediately close again (they are slow). Leading the membrane potential to become a bit more negative before its return to the resting state.
How can you interpret the following graph?
(source: Purves, D., Augustine, G. J., Fitzpatrick, D., Hall, W. C., LaMantia, A.-S., McNamara, J. O., & Williams, S. M. (Eds.). (2004). Neuroscience (3rd ed.). Sinauer Associates.)
These are the Na+ (red) and K+ (yellow) conductances (g) during an action potential.
The conductance of Na+ has an early peak and a quick decay. Whereas, the K+ conductance rises slower but decays slower.
After the peak in sodium conductance, the conductance of potassium is higher than that of sodium.
Therefore, the sharp rise in sodium conductance corresponds to the sharp depolarization of the membrane, while the slower activation of potassium conductance is responsible for the repolarization of the membrane.
What is the absolute refractory period?
This is a period during which it is impossible to fire another action potential, no matter how strong the stimulus. It is due to the inactivated sodium channels.
(source of the image: www.physiologyweb.com)
A biological membrane is a ________ because it ______ charge.
…capacitor…
…stores…
* A capacitor is a device that allows separation of electrical charge, so an electric potential (voltage) is established across its plates.
What is the difference between an ion channel and a transporter/pump?
Ion channels are pores in the cell membrane that passively transport ions from one side to the other down their concentration gradient.
Ion pumps perform active transport by moving ions against their concentration gradient. The pumps/transporters need energy (ATP) to do this.
A) Name the 3 main families of ion channels.
B) Which of these families do the K+ and Na+ channels belong to?
A)
- Ligand-gated
- Gap junctions
- Voltage-gated
B) Na+ and K+ channels are Voltage-Gated. They open at a specific voltage.
Name the technique used to study single ion channels.
The Patch-clamp technique. It allows high-resolution current recordings for a specific patch of membrane. That is useful because now scientists can focus on just a few ion channels at a time.
General procedure
- A glass pipette containing electrolyte solution is tightly sealed onto the cell membrane and thus isolates a membrane patch electrically. Currents fluxing through the channels in this patch flow into the pipette and can be recorded by an electrode that is connected to a highly sensitive differential amplifier.*
- In the voltage-clamp configuration, a current is injected into the cell via a negative feedback loop to compensate for changes in membrane potential. Recording this current allows conclusions about the membrane conductance.*
Image Source: https://www.leica-microsystems.com/science-lab/the-patch-clamp-technique/
What is the relative refractory period?
A period after the absolute refractory period, in which it is more difficult to trigger another action potential. However, a strong stimulus can cause another spike (sodium channels are de-inactivated).
(image source www.physiologyweb.com)
What would happen to EK if we increased intracellular [K+]?
EK becomes more negative
(test it!)
What would happen to EK if we increase extracellular [K+]?
EK becomes more positive.
What would happen to ECl if we increased intracellular [Cl-]?
ECl becomes more positive. (why?)
What is depicted in this diagram?
(image source: https://praneethnamburi.com/2015/02/05/simulating-neural-spike-trains/)
A raster plot.
Each dot in the plot represents a spike and each line in the plot represents one trial. Each row of spikes is called a spike train and represents the activity of the neuron for a specific time interval, here 1500 ms (or 1.5 seconds).
The average firing rate is called the baseline firing rate of a neuron, which is given in Hz (Hertz). Recall that Hz is the unit for frequency, given by
𝑓 = number of spikes / interval.
In this recording the baseline firing rate is 6Hz, meaning the neuron on average fires 6 spikes per second when no stimulus is presented (we get this number by taking the number of spikes and dividing by the number of trials and duration).
When a stimulus is presented, marked by the blue line, you see that there are many more lines! Now the neuron fires on average 30 spikes per second (30Hz).
Consider the figure and answer:
- the baseline firing frequency of the neuron below?
- the firing frequency after the stimulus presentation?
(image source: https://praneethnamburi.com/2015/02/05/simulating-neural-spike-trains/)
For this particular recording the baseline firing rate is 6Hz, meaning the neuron on average fires 6 spikes per second when no stimulus is presented (we get that by taking the average of lines of all neurons before the blue line).
When a stimulus is presented, marked by the blue line, you see that there are many more lines! Now the neuron fires on average 30 spikes per second (30Hz).
