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potassium channel lecture notes for class, Lecture notes of Neuroscience

potassium channel lecture notes for class

Typology: Lecture notes

2023/2024

Uploaded on 02/28/2024

jaydave-patel
jaydave-patel 🇺🇸

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Potassium Channels 1
Potassium channels are the most varied of all the electrolyte/ion channels with more than 50 types
discovered to date with over 80 different genes involved in coding for the subunits. Before we go
further into this, let’s define a couple of key concepts.
Inward rectification is the process of ions moving into the cells.
Outward rectification is the process of ions moving out of the cell.
When a channel is described as “inward rectifying” this means that the ions move more easily
through the channel into the cell. When a channel is described as “outward rectifying” this means the
opposite, ions move more easily out of the cell through the channel. So, the point is, that channels are
not simply conduits allowing ions to pass in either direction. The structure of the protein units
constituting the channels can make is easier for an ion to pass in one direction or another. To be sure,
the movement of ions is determined by the electrochemical forces that act on the electrolyte,
concentration gradient and electrical potential in accordance to the Nernst equation. Please review
these electrochemical forces from the earlier lectures if need be.
Applying the terms above, the voltage sensitive sodium channel could be described as “inward
rectifying” because is allows sodium to pass more easily into the cell compared to out of the cell. The
potentially confusing part of this is that most of the time the “inward or outward rectifying”
descriptors are not part of the “official name”. But some times it is, such as “inward rectifying
potassium channels”.
There are two broad categories of potassium channels, ones that are sensitive to voltage potential
relative to being open or closed, and others that are not.
A) Voltage sensitive potassium channels.
There are a number of voltage sensitive potassium channels, each with their own kinetic and voltage
dependent properties as well as pharmacological properties. Here are some of the types of voltage
sensitive potassium channels.
1) Transient outward current potassium channels. A few subtypes of these have been discovered.
Characteristically, then open rapidly in response to depolarization and then close rapidly. Important
function in cardiac muscle.
2) Delayed rectifying potassium channels. There are multiple subtypes of these, each with a different
functional profile and their own name. These channels are outward rectifying even though “outward
rectifying” it’s not in its name. These channels, as the name implies, open after a delayed time
relative to the time point of depolarization. Some of these open ultra-rapidly, others rapidly and other
slowly. All of these close slowly allowing potassium to efflux for a greater length to time compared
to the transient outward current potassium channels. These channels are found through the body,
neurons, kidney, muscle etc.
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Potassium channels are the most varied of all the electrolyte/ion channels with more than 50 types discovered to date with over 80 different genes involved in coding for the subunits. Before we go further into this, let’s define a couple of key concepts. Inward rectification is the process of ions moving into the cells. Outward rectification is the process of ions moving out of the cell. When a channel is described as “inward rectifying” this means that the ions move more easily through the channel into the cell. When a channel is described as “outward rectifying” this means the opposite, ions move more easily out of the cell through the channel. So, the point is, that channels are not simply conduits allowing ions to pass in either direction. The structure of the protein units constituting the channels can make is easier for an ion to pass in one direction or another. To be sure, the movement of ions is determined by the electrochemical forces that act on the electrolyte, concentration gradient and electrical potential in accordance to the Nernst equation. Please review these electrochemical forces from the earlier lectures if need be. Applying the terms above, the voltage sensitive sodium channel could be described as “inward rectifying” because is allows sodium to pass more easily into the cell compared to out of the cell. The potentially confusing part of this is that most of the time the “inward or outward rectifying” descriptors are not part of the “official name”. But some times it is, such as “inward rectifying potassium channels”. There are two broad categories of potassium channels, ones that are sensitive to voltage potential relative to being open or closed, and others that are not. A) Voltage sensitive potassium channels. There are a number of voltage sensitive potassium channels, each with their own kinetic and voltage dependent properties as well as pharmacological properties. Here are some of the types of voltage sensitive potassium channels. 1) Transient outward current potassium channels. A few subtypes of these have been discovered. Characteristically, then open rapidly in response to depolarization and then close rapidly. Important function in cardiac muscle. 2) Delayed rectifying potassium channels. There are multiple subtypes of these, each with a different functional profile and their own name. These channels are outward rectifying even though “outward rectifying” it’s not in its name. These channels, as the name implies, open after a delayed time relative to the time point of depolarization. Some of these open ultra-rapidly, others rapidly and other slowly. All of these close slowly allowing potassium to efflux for a greater length to time compared to the transient outward current potassium channels. These channels are found through the body, neurons, kidney, muscle etc.

3) Inward rectifying potassium channels. There are multiple subtypes of these, each with a different functional profile and their own name. As the name implies, these channels allow potassium to flow more easily into the cell comparted to out of the cell. But remember, potassium flow is contingent on electrochemical forces and the reversal potential as indicated by the Nernst equation. The only time potassium would flow into the cell would be if the potential of the cell membrane is more negative than the reversal potential, which rarely happens under normal physiological conditions. This category of channels are found throughout the body including neurons and muscle tissue. Below is a graft illustration potassium flow with an inward rectifying and outward rectifying channel. 4) M channels. These potassium channels open in response to depolarization causing potassium efflux. Sometimes this potassium efflux is called and “M current”. The name M come from the fact that these receptors can be inhibited by ACh binding to a muscarinic receptor leading to a cellular G-protein cascade which inhibits these channels. These channels are common in some neurons. B) Non-voltage sensitive potassium channels, i.e., channels that don’t open or close as a simple function of membrane voltage potential. Tandem pore domain potassium channel, aka, Two-pore-domain potassium channels, aka, leak channels We’ve discussed one of these potassium channels earlier. They are the potassium “leak channels” and serve as a major factor in setting the resting membrane potential. The degree of permeability of these leak channels are significantly less when compared to the outward rectifying potassium channels when the membrane is depolarized. In the literature they are called “Two-pore-domain potassium channels”. Despite the name, the channels don’t have “two pores”. These leak channels can be altered or regulated by oxygen tension, pH, G-protein activity, phosphorylation/dephosphorylation, mechanical stretch, and alteration the lipids associated with the channel. They can also be altered by pharmacological compounds. There are multiple subtypes of these channels. These are considered “non-gated” because they are always open in some degree, though the degree of openness can be altered by other factors as noted above. These channels are found throughout the body.

3) Calcium sensitive potassium channels These channels come in two categories. Potassium channels that are activated by the presence of calcium and those that can be activated by either change in membrane potential or the presence of calcium. The former are named SK channels as in “Small potassium”. These channels are call “small” because of the small amount of potassium the allow to flow when stimulated by calcium. The second type of channels are known at BK channels, as in “Big potassium” because of their ability allow large amounts of potassium to flow. These will respond to either voltage potential change or calcium. There are multiple subtypes of SK and BK channels. BK and SK channels are found throughout the body, neurons, kidney, smooth muscles etc. Closing comment: many potassium channels, volt dependent and ligand gated can be phosphorylated/dephosphorylated or interact with G-protein subunits. which can affect their function. Neurotransmitters, including neuropeptides, e.g., opioids, and influence the function of many ion channels including potassium channels through cellular processes.