Two-pore-domain potassium channel: Difference between revisions

Revision as of 23:59, 9 February 2025

Two-pore-domain potassium channel

Two-pore-domain potassium channels, also known as K2P channels, are a class of potassium channels that are characterized by having two pore-forming domains in each subunit. These channels are responsible for setting and regulating the resting membrane potential of cells and are involved in various physiological processes.

Structure

K2P channels are unique among potassium channels due to their structure, which includes two pore-forming domains per subunit. This structural feature allows them to form dimers, creating a functional channel with four pore domains. The channels are generally composed of four transmembrane segments and two pore loops, which contribute to the selectivity filter that allows potassium ions to pass through while excluding other ions.

Function

The primary function of two-pore-domain potassium channels is to maintain the resting membrane potential and contribute to the background potassium conductance in cells. They are often referred to as "leak" channels because they allow a constant, passive flow of potassium ions across the cell membrane. This flow is crucial for stabilizing the membrane potential and modulating cellular excitability.

K2P channels are involved in various physiological processes, including neuronal excitability, cardiac function, and pain perception. They are also sensitive to a range of physical and chemical stimuli, such as changes in pH, temperature, and mechanical stretch, which can modulate their activity.

Types

There are several subfamilies of K2P channels, each with distinct properties and regulatory mechanisms. Some of the well-known subfamilies include:

K2P1 (TWIK-1): The first identified member of the K2P family, involved in setting the resting membrane potential.
K2P2 (TREK-1): Known for its sensitivity to mechanical stretch and temperature changes.
K2P3 (TASK-1): Plays a role in pH sensing and is involved in respiratory control.

Clinical significance

Mutations and dysregulation of K2P channels have been implicated in various diseases, including neurological disorders, cardiac arrhythmias, and cancer. As such, they are considered potential targets for therapeutic intervention.

Related pages

References

@@ Line 1: / Line 1: @@
-'''Two-pore-domain potassium channels''' (K2P channels) are a family of [[potassium channel]]s that play a significant role in setting the resting membrane potential and regulating the excitability of neurons. Unlike other potassium channels, K2P channels possess two pore-forming domains and four transmembrane segments in each subunit, and they function as dimers. These channels are activated by various physical and chemical stimuli, including temperature, pH, mechanical stretch, and lipids, making them crucial for a wide range of physiological processes.
+== Two-pore-domain potassium channel ==
-== Structure and Function ==
+[[File:Two-pore_domain_potassium_channel_K2P1_PDB-3ukm.png|thumb|right|Structure of K2P1 channel]]
-K2P channels are characterized by their unique structure, which includes two pore-forming P domains in each subunit and a total of four transmembrane segments (M1, M2, M3, and M4). This configuration is distinct from the more common four-pore structure seen in other potassium channels. K2P channels function as dimers, with each dimer forming a complete channel with two pores. This structural arrangement allows K2P channels to contribute significantly to the background potassium conductance, helping to stabilize the resting membrane potential and control cell excitability.
+[[File:Two-pore_domain_potassium_channel_K2P2_PDB-4twk.png|thumb|right|Structure of K2P2 channel]]
+[[File:Two-pore_domain_potassium_channel_K2P3_PDB-6rv3.png|thumb|right|Structure of K2P3 channel]]
-== Classification ==
+Two-pore-domain potassium channels, also known as K2P channels, are a class of [[potassium channel]]s that are characterized by having two pore-forming domains in each subunit. These channels are responsible for setting and regulating the resting membrane potential of cells and are involved in various physiological processes.
-K2P channels are divided into several subfamilies based on their sequence similarity and functional properties. These include:
-* [[TREK]] (TWIK-Related K+ Channel)
+== Structure ==
-* [[TASK]] (TWIK-Related Acid-Sensitive K+ Channel)
-* [[TALK]] (TWIK-Related Alkaline pH-Activated K+ Channel)
-* [[THIK]] (Tandem Pore Domain Halothane-Inhibited K+ Channel)
-* [[TWIK]] (Tandem of P domains in a Weak Inward rectifying K+ channel)
-Each subfamily is sensitive to different physiological stimuli, which allows for a diverse range of functions across different cell types and tissues.
+K2P channels are unique among potassium channels due to their structure, which includes two pore-forming domains per subunit. This structural feature allows them to form dimers, creating a functional channel with four pore domains. The channels are generally composed of four transmembrane segments and two pore loops, which contribute to the selectivity filter that allows potassium ions to pass through while excluding other ions.
-== Physiological Roles ==
+== Function ==
-K2P channels are involved in many physiological processes, including the regulation of neuronal excitability, control of heart rate, and protection against ischemia. They are also implicated in the sensation of pain, mechanical sensing, and the response to anesthetics. Due to their sensitivity to a variety of stimuli, K2P channels serve as a critical link between cellular and systemic responses to environmental changes.
-== Clinical Significance ==
+The primary function of two-pore-domain potassium channels is to maintain the resting membrane potential and contribute to the background potassium conductance in cells. They are often referred to as "leak" channels because they allow a constant, passive flow of potassium ions across the cell membrane. This flow is crucial for stabilizing the membrane potential and modulating cellular excitability.
-Alterations in K2P channel function have been associated with several diseases, including depression, anxiety, epilepsy, and cancer. Drugs that modulate K2P channel activity are being explored as potential treatments for these conditions. For example, selective K2P channel openers could provide a new approach to pain management by reducing neuronal excitability without the side effects associated with traditional pain medications.
-== Research Directions ==
+K2P channels are involved in various physiological processes, including [[neuronal excitability]], [[cardiac function]], and [[pain perception]]. They are also sensitive to a range of physical and chemical stimuli, such as changes in pH, temperature, and mechanical stretch, which can modulate their activity.
-Ongoing research aims to further elucidate the structure-function relationships of K2P channels, their roles in disease, and their potential as therapeutic targets. Advanced techniques such as cryo-electron microscopy are being used to resolve the detailed structures of K2P channels, providing insights into their mechanism of action and how they are regulated by various stimuli.
+== Types ==
+There are several subfamilies of K2P channels, each with distinct properties and regulatory mechanisms. Some of the well-known subfamilies include:
+* '''K2P1 (TWIK-1)''': The first identified member of the K2P family, involved in setting the resting membrane potential.
+* '''K2P2 (TREK-1)''': Known for its sensitivity to mechanical stretch and temperature changes.
+* '''K2P3 (TASK-1)''': Plays a role in pH sensing and is involved in respiratory control.
+== Clinical significance ==
+Mutations and dysregulation of K2P channels have been implicated in various diseases, including [[neurological disorders]], [[cardiac arrhythmias]], and [[cancer]]. As such, they are considered potential targets for therapeutic intervention.
+== Related pages ==
+* [[Potassium channel]]
+* [[Ion channel]]
+* [[Membrane potential]]
+== References ==
+{{Reflist}}
+[[Category:Potassium channels]]
 [[Category:Ion channels]]
-[[Category:Membrane biology]]
-[[Category:Neuroscience]]
-{{Ion channel-stub}}