Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

Abstract

SummaryThe role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca 2 +-activated potassium channels (Pc,c,) and voltage-gated potassium channels (PK,v) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (Ib2 and interferon 3') are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,C~ and Pg.v. we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for Pg, v. Theses studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca2+-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

“…More emerging evidence suggest that K + channels play a crucial role in proliferation control in different cell types including corneal epithelial cells (Decoursey et al, 1987;Freedman et al, 1992;Day et al, 1993;Deutsch and Chen, 1993;Pappone and Ortiz-Miranda, 1993;Xu et al, 1996Xu et al, ,1999Wang et al, 1997;Roderick et al, 2003). The activation of K + channels is involved in the onset of cellular events associated with both T-and B-lymphocyte activation (Amigorena et al, 1990a,b;Lin et al, 1993). Enhanced K + channel expression or K + channel activity is associated with mitogenesis in several cell types (DeCoursey et al, 1984;Price et al, 1989).…”

“…Enhanced K + channel expression or K + channel activity is associated with mitogenesis in several cell types (DeCoursey et al, 1984;Price et al, 1989). Suppression of K + channel activity by blockers in culture significantly inhibits cell proliferation (Deterre et al, 1981;Amigorena et al, 1990b;Dubois and Rouzaire-Dubois, 1993;Lin et al, 1993). K + channel activity has been found to be a key determinant for cell progression through the G 1 checkpoint of the cell cycle (Lewis and Cahalan, 1990;Dubois and Rouzaire-Dubois, 1993;Xu et al, 1996;Roderick et al, 2003).…”

Modulation of Voltage-Dependent and Inward Rectifier Potassium Channels by 15-Epi-Lipoxin-A4 in Activated Murine Macrophages: Implications in Innate Immunity

“…In T cells, this crucial influx of Ca 2+ is only possible if they can keep their membrane potential negative by a counterbalance of K + efflux through K v 1.3 and/or K Ca 3.1 (38,57), and both channels are regarded as targets for immunosuppression (38). In the current study, we demonstrated that e-LXA 4 inhibits K v 1.3 in LPS-stimulated cells.…”

K+ Channel Expression during B Cell Differentiation: Implications for Immunomodulation and Autoimmunity

“…ϩ channels in T lymphocytes, the voltage-gated Kv1.3 channel (also known as KCNA3 (HUGO nomenclature)) and the Ca 2ϩ -activated IKCa1 channel (also known as KCNN4 (HUGO nomenclature); K Ca 3.1 (International Union of Pharmacology nomenclature) (1)), regulate Ca 2ϩ signaling by controlling the membrane potential of lymphocytes (2)(3)(4)(5)(6)(7). During activation, inositol 1,4,5-triphosphate generation induces the release of Ca 2ϩ from internal stores.…”