Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets

Abstract

TWIK-related acid-sensitive K+ (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K2P) 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 K2P 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.

Brief isoflurane administration as an adjunct treatment to control organophosphate-induced convulsions and neuropathology

“…Isoflurane activates TASK-1/3 channels with subsequent neuroprotective effects ( Liu et al, 2005 ; Yao et al, 2017 ). TASK-1/3 potassium channels are strongly expressed in neurons throughout the CNS ( Talley et al, 2001 ; Fan et al, 2022 ) as well as in mitochondria ( Szewczyk et al, 2009 ). Numerous studies have found isoflurane to have neuroprotective and cardioprotective properties in various injury models through actions on TASK-1/3 and other potassium channels ( Liu et al, 2005 ; Park et al, 2005 ; Khatibi et al, 2011 ; Taheri et al, 2014 ; Altay et al, 2020 ; Zhai et al, 2023 ).…”

Proton Mechanisms of Neurotransmission and Calcium Signalling for Impulse Initiation, Development and Propagation

“…The protons released by Glu, GABA or ACh acidify the inter-synaptic space and can activate acid-sensitive receptors at the postsynaptic termination together with specific receptors for Glu, GABA and ACh. There are numerous proton-sensitive receptors in the postsynaptic termination [139], both ionotropic such as ASICs [39,117], TRPV1 [41,[140][141][142], CaV3 [143] and metabotropic, of the TASK type [144] and GPCRs [43]. The proton activation of the postsynaptic receptor can foster the opening of ionic channels [103,145], depolarization and the generation of a new action potential, enabling the impulse to continue [23,59,146].…”

Proton Mechanisms of Neurotransmission and Calcium Signalling for Impulse Initiation, Development and Propagation

“…The protons released by Glu, GABA or ACh acidify the inter-synaptic space and can activate acid-sensitive receptors at the postsynaptic termination together with specific receptors for Glu, GABA and ACh. There are numerous proton-sensitive receptors in the postsynaptic termination, 138 both ionotropic such as ASICs, 39,116 TRPV1, 41,[139][140][141] CaV3 142 and metabotropic, of the TASK type 143 and GPCRs. 43 The proton activation of the postsynaptic receptor can foster the opening of ionic channels, 103,144 depolarization and the generation of a new action potential, enabling the impulse to continue.…”