Sunday, 6 March 2016

Potassium Channel to control T cells

Ohya S.Physiological Role of K(+) Channels in the Regulation of T Cell Function. Yakugaku Zasshi. 2016;136(3):479-83.

Potassium ion (K(+)) channels play an important role in the modulation of calcium ion (Ca(2+)) signaling via control of the membrane potential. In T-lymphocytes, the voltage-gated K(+) channel, KV1.3, and the intermediate-conductance Ca(2+)-activated K(+) channel, KCa3.1, predominantly contribute to K(+) conductance, and are responsible for cell proliferation, differentiation, apoptosis and infiltration. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, afflicts more than 0.1% of the population worldwide. In the chemically-induced IBD model mouse, an increase in KCa3.1 activity was observed in mesenteric lymph node CD4(+) T-lymphocytes, concomitant with an upregulation of KCa3.1 and a positive KCa3.1 regulator, NDPK-B. Pharmacological blockade of the KCa3.1 K(+) channel by TRAM-34 and/or ICA17043 elicited 1) a significant decrease in IBD severity, as assessed by diarrhea, visible fecal blood, inflammation and crypt damage of the colon; and 2) restoration of the expression levels of KCa3.1 and Th1 cytokines in CD4(+) T-lymphocytes in the IBD model. Recent studies have indicated the impact of K2P5.1 upregulation in T lymphocytes on the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The K2P5.1 K(+) channel is therefore highlighted as a potent therapeutic target in managing the pathogenesis of autoimmune diseases. Alternatively, pre-mRNA splicing of ion channels is associated with the development and progression of various diseases, including autoimmune diseases. Therefore, mRNA-splicing mechanisms underlying the transcriptional regulation of K2P5.1 K(+) channels may be a new strategic therapeutic target for autoimmune and inflammatory diseases.

We have heard alot about sodium channels as targets for neuroprotection but we will be hearing more about potassium channels. Some people think that KV1.4 is a target of autoimunity in MS.This study looks at other types of potassium channels, such as the intermediate conductance calcium activated potassium channels and finds that blockage of them can inhibit the development of autoimmnity and could be a new target. TheK2P5.1
is also known as TASK-2 and has been implicated in MS before

3 comments:

  1. How does Fampyra as a potassium channel blocker relate to this?

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  2. Most of cannabis based medicine target potassium channels, no? I remember a mouse doctor asking me for an hypothesis to support the use of THC based medicines as DMTs. Seems like the potassium channel modulation could be a good one.

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    Replies
    1. The cannabinoids act on a different potassium chanel type the inwardly rectify potassium channel. I think this channel is involved in resetting the nerve signal rather than stoping immune activation. But well spotted.

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