Expression and localisation of two-pore domain (K2P) background leak potassium ion channels in the mouse retina

Abstract

Two-pore domain (K2P) potassium channels perform essential roles in neuronal function. These channels produce background leak type potassium currents that act to regulate resting membrane potential and levels of cellular excitability. 15 different K2P channels have been identified in mammals and these channels perform important roles in a wide number of physiological systems. However, to date there is only limited data available concerning the expression and role of K2P channels in the retina. In this study we conduct the first comprehensive study of K2P channel expression in the retina. Our data show that K2P channels are widely expressed in the mouse retina, with variations in expression detected at different times of day and throughout postnatal development. The highest levels of K2P channel expression are observed for Müller cells (TWIK-1, TASK-3, TRAAK, and TREK-2) and retinal ganglion cells (TASK-1, TREK-1, TWIK-1, TWIK-2 and TWIK-3). These data offer new insight into the channels that regulate the resting membrane potential and electrical activity of retinal cells, and suggests that K2P channels are well placed to act as central regulators of visual signalling pathways. The prominent role of K2P channels in neuroprotection offers novel avenues of research into the treatment of common retinal diseases.

Melanopsin Phototransduction Is Repurposed by ipRGC Subtypes to Shape the Function of Distinct Visual Circuits

“…The sensitivity to extracellular Ba 2+ and ML 365 and insensitivity to arachidonic acid and chloroform is consistent with a specific modulation of the TASK subfamily of K2P channels, which is one of two K2P subfamilies that are closed by Gq activation (Mathie 2007). TASK K2P channels have previously been shown to be expressed in the ganglion cell layer of the retina, which combined with our pharmacological data, makes them a likely candidate for melanopsin modulation (Hughes et al, 2017).…”

Clinical Importance of the Human Umbilical Artery Potassium Channels

“…The 2-pore domain K + (K 2P ) channels were first identified in the late 1990s [ 98 , 99 ]. This channel family produces leak-type K + currents [ 100 ] and are involved in controlling and stabilizing MP and the levels of cellular excitability [ 1 , 100 , 101 ].…”

“…Structurally, K 2P channels are characterized by having two pore-forming regions (P1–P2) in each channel subunit, surrounded by four transmembrane-spanning (4TMS) helices and a large “cap” domain. Moreover, these channels are different from the remaining K + channels because they are the smallest, and they do not form tetrameters but functional dimers [ 1 , 100 , 102 ]. The K 2P channels elicit spontaneously active and outwardly rectifying “background leak”-type K + conductance.…”

“…Instead, two external blockers of these K + channels in arterial SM, anandamide 10 µmol/L [ 114 ] and zinc ion (Zn +2 ) 100 µmol/L [ 114 , 116 ], and two openers, halothane [ 114 ] and ONO-RS-082 [ 117 ], have been reported. Moreover, these channels are sensitive to important biophysical stimuli (e.g., pH, temperature, and mechanical pressure), and some of them are inhibited by the acidification of extracellular fluid [ 1 , 100 , 116 , 118 ]. The K 2P channels are also targets for drugs (including inhalational and local anesthetics, antipsychotics, antidepressants, and neuroprotective agents), and modulated by G protein signaling pathways and second messengers [ 103 , 104 , 106 , 107 , 119 , 120 ].…”

Trabecular Meshwork TREK-1 Channels Function as Polymodal Integrators of Pressure and pH

“…The 426-residue TREK-1 (TWIK-related potassium; OMIM 603219) channel subunit encoded by the human KCNK2 gene contains two pore-forming P domains and four transmembrane segments. Its expression covers the brain, heart, kidneys, ovaries, and eye, as well as smooth muscle cells and mechanosensitive neurons that innervate the colon and bladder 19–22. TREK-1 gating is inhibited by extracellular protons but somewhat uniquely among ion channels, the channel activity can be potentiated by intracellular protons 23.…”