Abstracts (complete list) - Wissenschaft Online

Sven Meuth, Stefan Bittner, Ole Simon, Heinz Wiendl
Tandem pore domain potassium channels TWIK-related acidsensitive
K+ channel 1 (TASK1) and TASK3 modulate effector
functions of T lymphocytes: a novel therapeutic target for Tcell
mediated autoimmune diseases
One decade ago, two-pore domain K+ channels (K2P), a new family of potassium
channels was described and has since then attracted much attention due to their unique
physiological properties. These potassium channels contribute to the resting membrane
potential and a rising diversity of regulatory mechanisms (e.g. pH drop or O2
deprivation) has been revealed. To date, little is known about their role on non-neuronal
cells and under pathological conditions.
We here investigate the role of the TWIK-related acid-sensitive potassium channels 1
(TASK1) and TASK3 on human T lymphocytes for T cell functions in vitro as well as their
pathogenic role in a model of multiple sclerosis (adoptive transfer experimental
autoimmune encephalomyelitis, AT-EAE). TASK1 and TASK3 are expressed on human T
lymphocytes as indicated by immunocytochemistry and western blotting procedures.
Pharmacological treatment (bupivacaine, anandamide, spermine and ruthenium red) of
isolated human CD3+ T cells revealed a dose dependent (~ 40%) reduction of an
outward current in whole-cell patch-clamp recordings indicative of TASK channels.
However, the same channel modulators significantly reduced IFNg production and
decreased proliferation rate of T cells after CD3/CD28 bead stimulation. Kv1.3, an
established potassium channel for T cell function, was used as control.
In the next step we addressed the question whether the importance of TASK channels
for T cell functions could as well be transferred into an in vivo model to demonstrate
their pathogenetic relevance. AT-EAE was evoked by MBP-specific T lymphocytes and
application of TASK channel inhibitors resulted in a delayed disease onset, milder
disease course and earlier recovery.
Taken together our data describe TASK channels as important mediators of T cell
function in vitro and in a model of multiple sclerosis in vivo underlining their potential
for immunotherapeutic strategies.