Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology

Herrera-Pérez, Salvador; Campos-Ríos, Ana; Rueda‐Ruzafa, Lola; Lamas, José Antonio

doi:10.3390/ijms22126635

Cited by 11 publications

(9 citation statements)

References 116 publications

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“…To date, 15 genes encoding a group of two-pore domain K + channels (K2P) have been identified in mammalian cells [ 159 , 271 ]. The synthesized proteins are distinguished by a unique subunit architecture with a molecular weight of approximately 70 kDa [ 270 , 272 , 273 ]. The group of K2P channels has been divided into 7 functional groups: TREK, TRAAK, TALK, TWIK, TASK, THIK, and TRESK.…”

Section: Modulators Of Mitochondrial Task Channelsmentioning

confidence: 99%

Alternative Targets for Modulators of Mitochondrial Potassium Channels

et al. 2022

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Mitochondrial potassium channels control potassium influx into the mitochondrial matrix and thus regulate mitochondrial membrane potential, volume, respiration, and synthesis of reactive oxygen species (ROS). It has been found that pharmacological activation of mitochondrial potassium channels during ischemia/reperfusion (I/R) injury activates cytoprotective mechanisms resulting in increased cell survival. In cancer cells, the inhibition of these channels leads to increased cell death. Therefore, mitochondrial potassium channels are intriguing targets for the development of new pharmacological strategies. In most cases, however, the substances that modulate the mitochondrial potassium channels have a few alternative targets in the cell. This may result in unexpected or unwanted effects induced by these compounds. In our review, we briefly present the various classes of mitochondrial potassium (mitoK) channels and describe the chemical compounds that modulate their activity. We also describe examples of the multidirectional activity of the activators and inhibitors of mitochondrial potassium channels.

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Section: Modulators Of Mitochondrial Task Channelsmentioning

confidence: 99%

Alternative Targets for Modulators of Mitochondrial Potassium Channels

et al. 2022

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“…New research in this area may improve our knowledge about K 2 P channel function. K 2 P channel family is really fascinating since several studies have demonstrated that the expression of TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 are dysregulated in AF [6,11,23,24,[31][32][33]. Moreover, the loss of function (LoF) mutations on TASK1-enconding gene have been reported in patients with familiar AF [34].…”

Section: Outlook K 2 P Channels In Atrialmentioning

confidence: 99%

Unraveling the Role of K2P Channels in Atrial Fibrillation

Mondéjar-Parreño¹

2022

Front. Biosci. (Schol Ed)

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Atrial fibrillation (AF) is a condition in which the electrical signals in the upper heart chambers (atria) are rapid and disorganized, producing an irregular and chaotical heartbeat. The sinus rhythm should be between 60 to 100 bpm at rest, while the heart rhythm in AF patients may be over 140 bpm. Either structural and electro-mechanical remodeling of the atrial tissue underlies the perpetuation and evolution of AF from the paroxysmal to persistent form. Unravelling the different pathological pathways involved in AF that lead to arrhythmogenesis and atrial remodeling is needed to discovery new and effective therapeutic approaches. A variety of drugs are available to convert and maintain the AF patient in a normal sinus rhythm; however, these strategies have limited chances of success or fail with the progression of AF to more persistent/permanent forms. Consequently, it is necessary to find new therapeutic targets for the relief of persistent or chronic AF forms, as well as the development of new and more effective pharmacological tools. The atrial specific two-pore domain K + channels (K2P) constitute the background K + current on atrial cardiomyocytes and modulate cell excitability emerging as novel targets in this disease and avoiding ventricle side effects. Moreover, several antiarrhythmic drugs used in AF treatment exert their mechanism of action in part by modulation of K2P channels. Thus far, TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 channel have been identified as responsible for background currents IK2P current in atrial cells; however, it is not excluded that other K2PX subunits or subfamilies have physiological roles in atria. To date, a great diversity openers, activators and blockers of K2P channel have been identified, particularly those targeting TASK and TREK channels. Several studies have demonstrated that the expression of TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 are dysregulated in AF and their pharmacology rescue could suppose a novel therapy in AF. The main objective is to examine the regulation of K2P channels and the current K2P channels pharmacological modulators for AF treatment.

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“…The general (patho)physiology of cardiac mechanosensitive K 2P channels has recently been reviewed in a comprehensive manner [128][129][130]. It has been reported that TREK-1 (but not TREK-2 or TRAAK) is expressed in the heart of several different species at the mRNA and protein level (for summary, see [128]).…”

Section: Mechanical Activation Of K 2p Channels In the Heartmentioning

confidence: 99%

Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

Lengyel

Enyedi

Czirják

2021

IJMS

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The two-pore domain K2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K2P subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K+ current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions. In the past decade, great advances have been made in the investigation of the molecular determinants of mechanosensation, and members of the TREK subfamily have emerged among the best-understood examples of mammalian ion channels directly influenced by the tension of the phospholipid bilayer. In parallel, the crucial contribution of mechano-gated TREK channels to the regulation of membrane potential in several cell types has been reported. In this review, we summarize the general principles underlying the mechanical activation of K2P channels, and focus on the physiological roles of mechanically induced hyperpolarization.

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Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology

Cited by 11 publications

References 116 publications

Alternative Targets for Modulators of Mitochondrial Potassium Channels

Alternative Targets for Modulators of Mitochondrial Potassium Channels

Unraveling the Role of K2P Channels in Atrial Fibrillation

Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

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