Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets
TWIK-related acid-sensitive K<sup>+</sup> (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K<sub>2P</sub>) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sens...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/23/8296 |
| _version_ | 1797462633037692928 |
|---|---|
| author | Xueming Fan Yongzhi Lu Guizhi Du Jin Liu |
| author_facet | Xueming Fan Yongzhi Lu Guizhi Du Jin Liu |
| author_sort | Xueming Fan |
| collection | DOAJ |
| description | TWIK-related acid-sensitive K<sup>+</sup> (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K<sub>2P</sub>) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods. They are similar to other K<sub>2P</sub> channels in that they can create and use background-leaked potassium currents to stabilize resting membrane conductance and repolarize the action potential of excitable cells. TASK channels are expressed in both the nervous system and peripheral tissues, including excitable and non-excitable cells, and are widely engaged in pathophysiological phenomena, such as respiratory stimulation, pulmonary hypertension, arrhythmia, aldosterone secretion, cancers, anesthesia, neurological disorders, glucose homeostasis, and visual sensitivity. Therefore, they are important targets for innovative drug development. In this review, we emphasized the recent advances in our understanding of the biophysical properties, gating profiles, and biological roles of TASK channels. Given the different localization ranges and biologically relevant functions of TASK-1 and TASK-3 channels, the development of compounds that selectively target TASK-1 and TASK-3 channels is also summarized based on data reported in the literature. |
| first_indexed | 2024-03-09T17:39:23Z |
| format | Article |
| id | doaj.art-21f15cf81bcf4cee9e502a7e3d63c702 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:39:23Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-21f15cf81bcf4cee9e502a7e3d63c7022023-11-24T11:39:52ZengMDPI AGMolecules1420-30492022-11-012723829610.3390/molecules27238296Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic TargetsXueming Fan0Yongzhi Lu1Guizhi Du2Jin Liu3Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, ChinaGuangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510700, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, ChinaTWIK-related acid-sensitive K<sup>+</sup> (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K<sub>2P</sub>) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods. They are similar to other K<sub>2P</sub> channels in that they can create and use background-leaked potassium currents to stabilize resting membrane conductance and repolarize the action potential of excitable cells. TASK channels are expressed in both the nervous system and peripheral tissues, including excitable and non-excitable cells, and are widely engaged in pathophysiological phenomena, such as respiratory stimulation, pulmonary hypertension, arrhythmia, aldosterone secretion, cancers, anesthesia, neurological disorders, glucose homeostasis, and visual sensitivity. Therefore, they are important targets for innovative drug development. In this review, we emphasized the recent advances in our understanding of the biophysical properties, gating profiles, and biological roles of TASK channels. Given the different localization ranges and biologically relevant functions of TASK-1 and TASK-3 channels, the development of compounds that selectively target TASK-1 and TASK-3 channels is also summarized based on data reported in the literature.https://www.mdpi.com/1420-3049/27/23/8296TASK channelsbiophysical propertiesgating profilesbiological rolestargeted compounds |
| spellingShingle | Xueming Fan Yongzhi Lu Guizhi Du Jin Liu Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets Molecules TASK channels biophysical properties gating profiles biological roles targeted compounds |
| title | Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets |
| title_full | Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets |
| title_fullStr | Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets |
| title_full_unstemmed | Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets |
| title_short | Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets |
| title_sort | advances in the understanding of two pore domain task potassium channels and their potential as therapeutic targets |
| topic | TASK channels biophysical properties gating profiles biological roles targeted compounds |
| url | https://www.mdpi.com/1420-3049/27/23/8296 |
| work_keys_str_mv | AT xuemingfan advancesintheunderstandingoftwoporedomaintaskpotassiumchannelsandtheirpotentialastherapeutictargets AT yongzhilu advancesintheunderstandingoftwoporedomaintaskpotassiumchannelsandtheirpotentialastherapeutictargets AT guizhidu advancesintheunderstandingoftwoporedomaintaskpotassiumchannelsandtheirpotentialastherapeutictargets AT jinliu advancesintheunderstandingoftwoporedomaintaskpotassiumchannelsandtheirpotentialastherapeutictargets |