The Volume Activated Potassium Channel KCNK5 is Up-Regulated in Activated Human T Cells, but Volume Regulation is Impaired

Abstract

Background/Aims: The potential role of the two-pore domain potassium channel KCNK5 (also known as TASK-2 and K_2P5.1) in activated T cell physiology has only recently been described. So far KCNK5 has been described to be up-regulated in T cells in multiple sclerosis patients and to be implicated in the volume regulatory mechanism regulatory volume decrease (RVD) in T cells. Methods: We investigated the time-dependent expression pattern of KCNK5 in CD3/CD28 activated human T cells using qPCR and Western blotting and its role in RVD using a Coulter Counter. Results: KCNK5 is highly up-regulated in CD3/CD28 activated T cells both at mRNA (after 24 h) and protein level (72 and 144 h), but despite this up-regulation the RVD response is inhibited. Furthermore, the swelling-activated Cl^- permeability in activated T cells is strongly decreased, and the RVD inhibition is predominantly due to the decreased Cl^- permeability. Conclusion: The up-regulated KCNK5 in activated human T cells does not play a volume regulatory role, due to decreased Cl^- permeability. We speculate that the KCNK5 up-regulation might play a role in hyperpolarization of the cell membrane leading to increased Ca²⁺ influx and proliferation of T cells.

Cell Volume Changes and Membrane Ruptures Induced by Hypotonic Electrolyte and Sugar Solutions

“…However, if the cell is exposed to the more severe and persistent osmolarity change, it preserves its integrity by additional mechanisms known by the expressions regulatory volume decrease (RVD) and regulatory volume increase (RVI) (Lang et al, 1998;Okada et al, 2001;Strange, 2004;Groulx et al, 2006). These mechanisms include the shape transformations and the flattening of the membrane invaginations (Echarri and Del Pozo, 2015;Echarri et al, 2019), the activation of additional membrane transport mechanisms (Jennings and Schulz, 1990;Sarkadi and Parker, 1991;Kirkegaard et al, 2016), and the upregulation of osmoregulatory proteins and molecular chaperonins to counteract the protein unfolding (Burg and Garcia-Perez, 1992;Caruccio et al, 1997). The channels that drastically increase the permeability of the cell membrane were believed to be ion-selective (Stutzin et al, 1999;Culliford et al, 2004); however, many studies indicate that smaller organic osmolytes can also pass through these channels (Jackson and Strange, 1993;Strange and Jackson, 1995;Hall et al, 1996).…”

Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity

“…For instance, Btn2a2 and potassium-channel subfamily K member 5 ( Kcnk5 ), which were under-expressed in the three resistant clones, have been shown to participate in T-cell mediated immunity. 48 , 86 Microtubule-associated protein 1A ( Map1a ) and carnitine palmitoyltransferase 1C ( Cpt1c ) promote HIV-1 routing to the nucleus and viral replication. 87 , 88 Carbonyl Reductase 1 ( Cbr1 ) is an anti-inflammatory mediator, 89 Phosphoinositide-3-Kinase regulatory subunit 5 ( Pik2r5 ) is an inflammation-related gene with a prognostic value for lung adenocarcinoma, 90 , 91 and cardiotrophin 1 ( Ctf1 ) an immune-related gene belonging to the IL-6 family.…”

Water Homeostasis and Cell Volume Maintenance and Regulation

“…Because the volume-sensitive K + channel is pH-sensitive and has a small ion conductance, TASK-1 and TASK-2 channels expressed in Ehrlich cells (Niemeyer, et al, 2000) were proposed as candidates (Hougaard, Jørgensen & Hoffmann, 2001). The TASK-2 channel was later shown to be a major component of the K + conductance activated by cell swelling (Kirkegaard, Lambert, Gammeltoft & Hoffmann, 2010; Kirkegaard, Strøm, Gammeltoft, Hansen & Hoffmann, 2016). KCNQ4, but not KCNQ2/3, were also shown to be involved in regulatory volume decrease in HEK293 cells overexpressing these channels (Hougaard, Klaerke, Hoffmann, Olesen & Jorgensen, 2004).…”