The Pharmacology of Two-Pore Domain Potassium Channels

Kamuene, Jordie M.; Xu, Yu; Plant, Leigh D.

doi:10.1007/164_2021_462

Cited by 12 publications

(7 citation statements)

References 125 publications

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“…The family of two-pore domain K + channels (K2P) is composed of 15 different subunits (K2P1–7, K2P9–10, K2P12–13 and K2P15–18) [ 113 ]. They are responsible for a voltage-independent K + -selective leak that is regulated by numerous chemical and physiological stimuli such as pH, mechanical stretch, temperature, membrane phospholipid composition, second messengers or activation of G protein-coupled receptors (GPCRs) [ 113 , 131 ]. These channels play a central role in Em regulation in a wide range of cell types [ 131 ].…”

Section: Sperm Capacitation and Hyperpolarizationmentioning

confidence: 99%

“…They are responsible for a voltage-independent K + -selective leak that is regulated by numerous chemical and physiological stimuli such as pH, mechanical stretch, temperature, membrane phospholipid composition, second messengers or activation of G protein-coupled receptors (GPCRs) [ 113 , 131 ]. These channels play a central role in Em regulation in a wide range of cell types [ 131 ]. K2P subunits have a structure unique among K + channels, with 4 TM, and the functional channel is formed by two 2P dimers, leading, in a similar way to other K + channels, to a tetramer-like structure [ 113 ].…”

Section: Sperm Capacitation and Hyperpolarizationmentioning

confidence: 99%

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The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function

Pinto

Odriozola

Candenas

et al. 2023

IJMS

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During the last seventy years, studies on mammalian sperm cells have demonstrated the essential role of capacitation, hyperactivation and the acrosome reaction in the acquisition of fertilization ability. These studies revealed the important biochemical and physiological changes that sperm undergo in their travel throughout the female genital tract, including changes in membrane fluidity, the activation of soluble adenylate cyclase, increases in intracellular pH and Ca2+ and the development of motility. Sperm are highly polarized cells, with a resting membrane potential of about −40 mV, which must rapidly adapt to the ionic changes occurring through the sperm membrane. This review summarizes the current knowledge about the relationship between variations in the sperm potential membrane, including depolarization and hyperpolarization, and their correlation with changes in sperm motility and capacitation to further lead to the acrosome reaction, a calcium-dependent exocytosis process. We also review the functionality of different ion channels that are present in spermatozoa in order to understand their association with human infertility.

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Section: Sperm Capacitation and Hyperpolarizationmentioning

confidence: 99%

Section: Sperm Capacitation and Hyperpolarizationmentioning

confidence: 99%

The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function

Pinto

Odriozola

Candenas

et al. 2023

IJMS

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“…There may be various K2P channels subtypes expressed in a given cell, but this has yet to be investigated. The research around K2P channels subtypes and pharmacological profiles is growing [ 22 , 36 , 37 , 38 , 39 , 40 , 41 ] but there is still much to be learned about these channels particularly related to disease states [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…There appear to be 15 known types of K2P channels in humans and 11 known types in Drosophila [ 34 , 35 ]. There has been some renaming of the subtypes based on function and pharmacology, but basically there are six subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK) [ 22 , 36 , 37 , 38 , 39 , 40 , 41 ]. Specifically, TASK-3 misexpression is related with cancer [ 42 ] and forms of epilepsy [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Hyperpolarization Induced by Lipopolysaccharides but Not by Chloroform Is Inhibited by Doxapram, an Inhibitor of Two-P-Domain K+ Channel (K2P)

Cooper

Krall

2022

IJMS

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Bacterial septicemia is commonly induced by Gram-negative bacteria. The immune response is triggered in part by the secretion of bacterial endotoxin lipopolysaccharide (LPS). LPS induces the subsequent release of inflammatory cytokines which can result in pathological conditions. There is no known blocker to the receptors of LPS. The Drosophila larval muscle is an amendable model to rapidly screen various compounds that affect membrane potential and synaptic transmission such as LPS. LPS induces a rapid hyperpolarization in the body wall muscles and depolarization of motor neurons. These actions are blocked by the compound doxapram (10 mM), which is known to inhibit a subtype of the two-P-domain K+ channel (K2P channels). However, the K2P channel blocker PK-THPP had no effect on the Drosophila larval muscle at 1 and 10 mM. These channels are activated by chloroform, which also induces a rapid hyperpolarization of these muscles, but the channels are not blocked by doxapram. Likewise, chloroform does not block the depolarization induced by doxapram. LPS blocks the postsynaptic glutamate receptors on Drosophila muscle. Pre-exposure to doxapram reduces the LPS block of these ionotropic glutamate receptors. Given that the larval Drosophila body wall muscles are depolarized by doxapram and hyperpolarized by chloroform, they offer a model to begin pharmacological profiling of the K2P subtype channels with the potential of identifying blockers for the receptors to mitigate the actions of the Gram-negative endotoxin LPS.

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“…Based on their functional properties K 2P channels can be subdivided into subfamilies of weakly inward rectifying (TWIK), TWIK-related (TREK), acid-sensitive (TASK), arachidonic acid-sensitive (TRAAK), alkaline-activated (TALK), halothane-inhibited (THIK) and TWIKrelated spinal cord (TRESK) K + channels (Fig. 1D) [24]. The last identified K 2P channel is TRESK, which was found in 2003 by analysis of the human genome data base [25].…”

Section: Introduction -The K 2p Channel Familymentioning

confidence: 99%

The Special One: Architecture, Physiology and Pharmacology of the TRESK Channel

Schreiber

Düfer

Seebohm

2022

Cell Physiol Biochem

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The TWIK-related spinal cord K+ channel (TRESK) is part of the two-pore domain K+ channel family (K2P), which are also called leak potassium channels. As indicated by the channel family name, TRESK conducts K+ ions along the concentration gradient in a nearly voltage-independent manner leading to lowered membrane potentials. Although functional and pharmacological similarities exist, TRESK shows low sequence identity with other K2P channels. Moreover, the channel possesses several unique features such as its sensitivity to intracellular Ca2+ ions, that are not found in other K2P channels. High expression rates are found in immune-associated and neuronal cells, especially in sensory neurons of the dorsal root and trigeminal ganglia. As a consequence of the induced hyperpolarization, TRESK influences neuronal firing, the release of inflammatory mediators and the proliferation of distinct immune cells. Consequently, this channel might be a suitable target for pharmacological intervention in migraine, epilepsy, neuropathic pain or distinct immune diseases. In this review, we summarize the biochemical and biophysical properties of TRESK channels as well as their sensitivity to different known compounds. Furthermore, we give a structured overview about the physiological and pathophysiological impact of TRESK, that render the channel as an interesting target for specific drug development.

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The Pharmacology of Two-Pore Domain Potassium Channels

Cited by 12 publications

References 125 publications

The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function

The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function

Hyperpolarization Induced by Lipopolysaccharides but Not by Chloroform Is Inhibited by Doxapram, an Inhibitor of Two-P-Domain K+ Channel (K2P)

The Special One: Architecture, Physiology and Pharmacology of the TRESK Channel

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