Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes

h3ro

Active Member
https://biolres.biomedcentral.com/articles/10.1186/s40659-016-0087-2


Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients

  • T. Nguyen,
  • D. Staines,
  • B. Nilius,
  • P. Smith and
  • S. Marshall-Gradisnik


Biological Research201649:27
DOI: 10.1186/s40659-016-0087-2

© The Author(s) 2016


Received: 26 January 2016

Accepted: 9 May 2016

Published: 31 May 2016



Abstract

Background
Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19+ B cells, CD56bright and CD56dim cell populations from CFS/ME patients.

Results
TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56bright TRPM3 35.72 % ± 7.37; CD56dim 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19+ B cells (1.56 ± 0.191) and CD56bright NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19+ B lymphocytes. CD56bright NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients.

Conclusions
The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.

Keywords
Chronic fatigue syndrome Transient receptor potential Calcium signalling Myalgic encephalomyelitis
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
https://biolres.biomedcentral.com/articles/10.1186/s40659-016-0087-2


Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients

  • T. Nguyen,
  • D. Staines,
  • B. Nilius,
  • P. Smith and
  • S. Marshall-Gradisnik


Biological Research201649:27
DOI: 10.1186/s40659-016-0087-2

© The Author(s) 2016


Received: 26 January 2016

Accepted: 9 May 2016

Published: 31 May 2016



Abstract

Background
Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19+ B cells, CD56bright and CD56dim cell populations from CFS/ME patients.

Results
TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56bright TRPM3 35.72 % ± 7.37; CD56dim 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19+ B cells (1.56 ± 0.191) and CD56bright NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19+ B lymphocytes. CD56bright NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients.

Conclusions
The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.

Keywords
Chronic fatigue syndrome Transient receptor potential Calcium signalling Myalgic encephalomyelitis
I love hearing about ion channels! I wrote a blog on a neurological channelopathy in ME/CFS when I was with PR. A fascinating topic. Ion channels are big in chronic pain by the way. Glad the Aussies are digging into this.


Based on the information in the Chaudhuri paper calcium channelopathies appear to be particularly associated with fatigue. Six of the eight neurological diseases associated with fatigue cited by the authors involve calcium channel abnormalities. The authors note a calcium channel blocker, nimodipine, is partially effective in treating myalgia in CFS (Chaudhuri et. al. 2000).

There is some evidence for increased intracellular calcium levels in CFS patients. Decreased serum calcium levels were associated with poor NK cell function and increased RNase L fragmentation in CFS patients. That they did not display the increased serum potassium levels expected in a calcium channelopathy, however, cast doubt on whether the increased calcium levels were due to a channelopathy.
The symptoms of CFS patients display some similarities to those found in neurological channelopathies

One of the symptoms CFS has in common with ion channel disorders is its fluctuating nature. All known channelopathies of the excitable tissues result in episodic episodes of fatigue. As in CFS some cause symptoms that indicate both peripheral and central disruption.

Neurological channelopathies (hyopakalemic periodic paralysis, episodic ataxia) are often characterized by sudden attacks of fatigue, weakness, cramping or even paralysis. As in CFS many channelopathies can be induced by physical activity and/or stress.

CFS patients share with epileptics a predisposition to several autonomic related symptoms such as frequent near syncope (fainting) and low blood pressure, particularly during TILT table testing.

CFS patients share with migraine sufferers such symptoms as headache, confusion, increased sensitivity to lights, sounds and smells as well as exacerbated responses to serotonin. Symptom exacerbation during menstruation and muscle pain, disequilibrium and unusual sweating are often seen in both diseases.
White brain matter abnormalities and reduced cerebral blood flows are also seen in both diseases and stress, alcohol and caffeine can exacerbate symptoms in both diseases. Transient or chronic fatigue is also common in migraine.
 

Forum Tips

Support Our Work

DO IT MONTHLY

HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT

Shopping on Amazon.com For HR

Latest Resources

Top