Author Topic: Channelopathies  (Read 6048 times)

G-man

  • Full Member
  • ***
  • Posts: 109
Channelopathies
« on: September 01, 2014, 12:50:56 AM »
I found an interesting article on channelopathies. It's too long and technical to post here, so I'll post the intro and the part relating to the immune system. I hope other people will find this info useful in the search to understand POIS.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935107/

"Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases."

"Channelopathies are diseases that develop because of defects in ion channels caused by either genetic or acquired factors. Mutations in genes encoding ion channels, which impair channel function, are the most common cause of channelopathies. Consistent with the distribution of ion channels throughout the human body, ion channel defects have been implicated in a wide variety of diseases, including epilepsy, migraine, blindness, deafness, diabetes, hypertension, cardiac arrhythmia, asthma, irritable bowel syndrome, and cancer.

There are remarkable causal heterogeneity (especially genetic) and phenotypic variability in channelopathies, which make the diseases challenging to classify. This review will categorize channelopathies based on the organ system with which they are predominantly associated in both clinical and pathophysiological respects. Nomenclature of genetic diseases described in this article can be found at the Online Mendelian Inheritance in Man (OMIM) website:http://www.ncbi.nlm.nih.gov/omim."

"Ion channels are transmembrane proteins that allow the passive flow of ions, both in and out of cells or cellular organelles, following their electrochemical gradients. Because the flux of ions across a membrane results in electrical currents, ion channels play a key role in generating membrane potential and function in diverse cellular activities, such as signal transduction, neurotransmitter release, muscle contraction, hormone secretion, volume regulation, growth, motility, and apoptosis. Ion channels can be classified according to the types of ions passing through them, the factors of their gating, their tissue expression patterns, and their structural characteristics. Ion channels typically exist in one of the three states: open, inactivated closed (refractory period), and resting closed. The gating (opening and closing) of ion channels is controlled by diverse factors, such as membrane potential (voltage), ligands (e.g., hormones and neurotransmitters), second messengers (e.g., calcium and cyclic nucleotides), light, temperature, and mechanical changes. Ion channels are formed from either a single protein (e.g., cystic fibrosis transmembrane conductance regulator, a chloride channel) or, more commonly, from an assembly of several subunits, each a protein encoded by a different gene. More than 400 ion channel genes have been identified. Further diversity comes from a number of mechanisms, which include the use of multiple promoters, alternative splicing, posttranslational modifications, heteromeric assembly of different principal subunits, and interaction with accessory proteins."

"Antibodies against ion channels and associated proteins expressed on the surface of neurons or muscle cells have been implicated in a variety of neurological pathologies ranging from myasthenia gravis (MG) to certain forms of encephalitis. Typical paraneoplastic antibodies generally target intracellular antigens and are not likely pathogenic. However, antibodies responsible for autoimmune channelopathies, often arising under paraneoplastic conditions, directly affect the kinetics and/or membrane density of ion channels or damage cells expressing the channels, which accounts for the favorable response shown by most patients to immunotherapies. Autoimmune channelopathies have been increasingly found in all age group.

MG is the prototype of autoimmune channelopathies. Most MG patients have autoantibodies against muscle nAChRs expressed on the postsynaptic membrane of muscle cells. These antibodies reduce functional nAChRs by direct block of function, complement-mediated damage to the cell membrane, and increased receptor endocytosis and degradation (a process referred to as antigenic modulation). Antibodies against MuSK, which is required for nAChR clustering, have been identified in a subset of MG patients without nAChR antibodies, reminiscent of the pathogenesis of certain cases of congenital myasthenic syndrome that is a clinically similar but distinct disorder (see p. 5).

Autoimmune autonomic ganglionopathy (AAG, also called autoimmune autonomic neuropathy) is an acquired form of autonomic neuropathies in which autoantibodies bind to the ?3 subunit of the neuronal nAChR located in ganglionic synapses of sympathetic, parasympathetic, and enteric nervous systems. Patients present with symptoms of diffuse autonomic failure, such as orthostatic hypotension, hypohidrosis, fixed and dilated pupils, dry eyes and mouth, urinary retention, and constipation or diarrhea. Ganglionic nAChRs mediate fast synaptic transmission in autonomic ganglia. Autoantibodies against ganglionic nAChRs impair cholinergic synaptic transmission, leading to the consequent symptoms of autonomic failure in AAG.

Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic disorder that is characterized by proximal muscle weakness, autonomic dysfunction, and areflexia. LEMS results from an autoimmune process in which autoantibodies react against presynaptic P/Q type voltage-gated calcium channels (VGCCs). Presynaptic VGCCs are involved in the depolarization-induced calcium influx that causes neurotransmitter release from nerve terminals. Autoantibodies against VGCCs are known to deplete the channels, reduce calcium influx, and cause a reduction of acetylcholine release. Approximately 50% of patients with LEMS have an underlying malignancy, such as small cell lung cancer (SCLC) in which SCLC cells express VGCCs on their surface, suggesting a cross reactivity of antibodies with presynaptic VGCCs. Accumulating evidence indicates that VGCCs also play a pathogenic role in certain patients with paraneoplastic cerebellar degeneration associated with SCLC.

Neuromyotonia (NMT) is a form of peripheral nerve hyperexcitability that is characterized by muscle fasciculations, cramps, pseudomyotonia (slow relaxation following muscle contraction), hyperhidrosis, and variable paraesthesias. NMT can be inherited or acquired. Evidence of a channelopathy can be found in one type of acquired NMT, called Isaac syndrome, in which autoantibodies are directed against ?-dendrotoxin (?-DTX)-sensitive voltage-gated potassium channel (VGKC) complexes expressed in motor and sensory nerves. The ?-DTX-sensitive VGKC complex consists of a VGKC (a Kv1 tetramer with auxiliary ? subunits) and associated proteins, such as leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein 2 (CASPR2), and contactin-2. VGKCs help repolarize depolarized cells and prevent repetitive discharges. Autoantibodies against components of VGKC complexes result in loss of functional VGKCs, reduced outward potassium currents, and spontaneous repetitive firing of action potentials, which leads to peripheral nerve hyperexcitability and enhanced muscle contraction. A combination of NMT and CNS manifestations (e.g., insomnia, confusion, hallucination, delirium, and amnesia) can be detected in Morvan syndrome, in which most patients have VGKC complex antibodies, predominantly against CASPR2. Cramp-fasciculation syndrome is another phenotype of peripheral nerve hyperexcitability that can be caused by VGKC complex antibodies, and this disease is characterized by the occurrence of severe muscle ache, cramps, and twitching in otherwise healthy individuals.

Limbic encephalitis (LE) is the most common CNS syndrome associated with increased levels of VGKC complex antibodies. LE is characterized by acute or subacute amnesia, confusion, seizures, and personality change or psychosis, with a high signal in the medial temporal lobes on MRI (indicating swelling and/or inflammation). Autoantibodies against ion channels other than VGKC have also been reported in LE patients, including antibodies against ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), GABAB receptor, and N-methyl-D-aspartate receptor (NMDAR). LE can arise as a paraneoplastic syndrome. Most LE patients have antibodies against the LGI1 component of VGKC complexes and do not usually have a tumor, whereas a small proportion of LE patients have CASPR2 antibodies and display an increased incidence of thymomas.

Anti-NMDAR encephalitis is characterized by sequential clinical manifestations that proceed from psychosis, amnesia, confusion, dysphasia, and seizures into dyskinesias, and autonomic and breathing instability, typically requiring management in the intensive care unit. Anti-NMDAR encephalitis is recognized as the most prevalent antibody-associated encephalitis and the second most common immune-mediated encephalitis after acute disseminated encephalomyelitis. A substantial proportion of patients with this disease are children and young adults with or without an associated tumor. The frequency of underlying tumors (usually ovarian teratoma) depends on age and sex and is lower in younger patients. Patients have antibodies against the NMDAR in blood and cerebrospinal fluid and exhibit high intrathecal synthesis of the antibodies. The NMDAR, a non-selective cation channel, is a glutamate receptor that modulates excitatory neurotransmission and synaptic plasticity in the CNS and plays a critical role in memory, learning, mood, and behavior. Anti-NMDAR antibodies have been demonstrated to lower the membrane density of postsynaptic NMDARs by enhancing receptor internalization and degradation, which can lead to reduced excitability of GABAergic neurons expressing NMDARs at high levels and to the deregulation of excitatory pathways. In more than 50% of patients with systemic lupus erythematosus (SLE), autoantibodies that react with NMDARs also cause neurological and psychological manifestations, which are often described as neuropsychiatric SLE.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disorder that primarily affects the optic nerves and spinal cord. Patients develop symptoms of optic neuritis and transverse myelitis, including blindness, paralysis, sensory defects, and bladder dysfunction, with frequent relapse and increasing disability. Most patients have autoantibodies against aquaporin-4 (AQP4), the main water channel in the CNS that is predominantly expressed on astrocytes. Astrocytes perform many important functions in the CNS, including the regulation of neurotransmission, immune responses, blood flow, and energy metabolism, and the maintenance of the blood-brain barrier (BBB). Autoantibodies against AQP4 have been suggested to induce complement-mediated astrocyte damage, local inflammatory reactions, and BBB disruption. These initial reactions are predicted to lead to oligodendrocyte injury, demyelination, neuronal damage, and the subsequent clinical manifestations of NMO. Alternative underlying mechanisms for the disorder have also been proposed, including antibody-mediated internalization of AQP4s and glutamate transporters, and antibody-induced activation of effector cells, such as natural-killer cells, which cause cytotoxicity in astrocytes."
31 years old. POIS since puberty. Cognitive and physical symptoms.

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #1 on: June 11, 2021, 03:28:12 PM »
https://www.reddit.com/r/POIS/comments/ninfii/i_could_potentially_have_this_but/

Quote from: brittneystaubin
For 24+ hours after masturbating (all external, not internal), I get very faint/lightheaded, as well as the symptoms of: fatigue, nausea, brain fog and inability to concentrate, low or no appetite, a small headache, and an intense bloating and tingling pressure in my uterus area. It gets worse immediately after eating anything (both the bloating and the weird pressure). But I am not able to drive the next day from this. I also have POTS and IBS-C.

I believe Voltage-gated sodium-selective ion channel NaV1.5 mutations can play a role in both syndromes.

swell

  • Sr. Member
  • ****
  • Posts: 263
Re: Channelopathies
« Reply #2 on: June 12, 2021, 08:53:52 PM »
Wow, I have a very long list of polymorphisms for the SCN5A gene (i.e. Nav 1.5 mutation you mention)
Just a few are: rs1805124 (CC), 6% have
rs11710077 (TT), 2% have
rs12053903 (TT), 26% have
rs1805126 (AA), 28% have
rs11129795(GG), 68% have
rs6763048 (AA), 76% have
Implications for me:  Decreases QRS durations, QT intervals, PR intervals (these are heart electrical conduction issues)
Would you know by chance, are these mutations associated with a decreased SCN5A or increased?  (Knowing that, we can figure out what benefits us or harms us).  Fyi: I do get sick, if I do salt gargles, weirdly, though I do otherwise consume dietary salt just fine.

I believe Voltage-gated sodium-selective ion channel NaV1.5 mutations can play a role in both syndromes.
« Last Edit: June 13, 2021, 03:00:19 PM by swell »
POIS Free, 1+ yrs despite daily o's (with occasional pois episodes)
Pois symptoms: Peripheral (Skin: Urticaria, dryness, pale blotchy skin), Exasperation of: [Nerve weakness, Muscle weakness + Mental (CNS: Brain Fog, Irritation, Isolation, Speech lethargy, Anxiety)].
Other conditions: ASD, ADD, GA

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #3 on: June 13, 2021, 06:48:38 AM »
5) Hmm, I don't think so. The only health problems I've had in my life are my soy allergy and an extreme sensitivity to cold (I never catch a cold or the flu from somebody else, but going outside in winter without four or five layers of clothes mean I'm going to get sick, 100% guaranteed). I also have very bad acne, I've had it since my first period, and I believe it's POIS-related because it gets noticeably worse during an episode.

Hi Fox, and welcome to the forum !
..
Talking about healthy gut, did you tried some probiotics supplements with both strains of lactobacillus and strains of bifidus ?..
...because taking potassium really helps with my fatigue, both for POIS and after physical...
No I did not try probiotics yet. Currently my GI- and POIS-symptoms are also very low. In my case gluten-free did the most change, perhaps clyndamycin helped a bit too. For a few years I tried gluten-free also without the same much difference perhaps due to bacterial overgrowth.

I eat 2-3 bananas each day as a source of potassium :)

Interestingly talking about potassium, I can induce some muscle weakness by eating too much liqorice (which is in these black candies). Liqorice has the potential to lower potassium. So potassium balance may be important also.

Triggers, in descending order of resulting symptom severity
  • Hard exercise
  • Orgasm
  • Moderate exercise
  • Stress
  • Very hot or cold weather
  • Certain foods (e.g. wheat, excessive sugar, alcohol)
Family health issues and facts
My father has Raynaud's disease, and struggles to keep his hands warm during Norwegian winter. Not sure if connected, but I also struggle with cold extremities and what feels like poor circulation. See symptom list above.

The can-not-stand-and-need-to-sit-down feeling that normally goes OK after eating salty snack + sugary isotonic drink...

Comment august data
Release of cytokines need intracellular calcium, they all go down post O. Is there a decrease of intracellular calcium inside leukocytes?

A lot of electrolytes intake before, during and after sport.  I take slightly salted water during sport ( 2 ml of salt in 600ml of water, approx.), I take 400ml of organic coconut water just after playing ( a great source of potassium and magnesium - it is like a natural "gatorade", but without the coloring and artificial flavors...), I eat a banana just after, too, for the potassium, and on top of that, I take 8 to 16 mEq of potassium in supplement form.

Just slept 17 hours (along with my TRT/Benadryl/Tylenol protocol above) to cut POIS recovery time.

2nd time I’ve done this. Seems to work.

90% POIS-free this way.

Temp list:

TRPM8 polymorphisms associated with increased risk of IBS-C and IBS-M

The TRPM8 Protein Is a Testosterone Receptor: I. BIOCHEMICAL EVIDENCE FOR DIRECT TRPM8-TESTOSTERONE INTERACTIONS

TRPM8 channels: A review of distribution and clinical role

Testosterone: a vascular hormone in health and disease.

Ion channel modulation chapter:
 
The key mechanism underlying the potential vasodilatory actions of testosterone has been proposed by several studies to involve an effect on smooth muscle cell ion channel function, influencing either potassium (K) channel opening and/or calcium (Ca2) channel inactivation.
 
Indeed, it was further demonstrated in electrophysiological patch-clamp studies that testosterone at increasing physiological concentrations can dose dependently inactivate L-type voltage-operated Ca2 channels, preventing Ca2 influx in rat A7r5 VSMCs (Hall et al. 2006; Fig. 4b). When combined with 10 nM testosterone, the treatment of cells with the well-known L-type voltagegated Ca2 channel blocker nifedipine (a commonly used anti-anginal and anti-hypertensive agent) at its maximally effective dose produced no further suppression of Ca2 influx, suggesting that testosterone acts at the same site as nifedipine.These data thereby support a beneficial role for testosterone as an endogenous L-Ca2 channel blocker


Testosterone-androgen receptor: The steroid link inhibiting TRPM8-mediated cold sensitivity

Ion channels regulating mast cell biology

Different triggers are classically associated with different syndromes, although these may vary within a given syndrome based on the specific mutation, as with LQTS. ???
Inherited arrhythmias: The cardiac channelopathies

Triggers:
Ion channels typically exist in one of the three states: open, inactivated closed (refractory period), and resting closed. The gating (opening and closing) of ion channels is controlled by diverse factors, such as membrane potential (voltage), ligands (e.g., hormones and neurotransmitters), second messengers (e.g., calcium and cyclic nucleotides), light, temperature, and mechanical changes.

cold:
https://poiscenter.com/forums/index.php?topic=3611.0

PE:
Significance of piezo-type mechanosensitive ion channel component 2 in premature ejaculation: An animal study
« Last Edit: June 13, 2021, 10:00:12 AM by Muon »

Iwillbeatthis

  • Sr. Member
  • ****
  • Posts: 499
Re: Channelopathies
« Reply #4 on: June 14, 2021, 11:18:12 AM »
Just saw now that I am homozygous for the SLC6A2 Gene -Norepinephrine Transporter

"This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]"

Seems pretty relevant to my symptoms and POIS

swell

  • Sr. Member
  • ****
  • Posts: 263
Re: Channelopathies
« Reply #5 on: June 15, 2021, 01:40:15 PM »
Congrats, is that not exciting :)  By the way, you need to put your SNP's with allele's (aka variants) for it to be a meaningful. Once we find snips (SNP's) with respective change (allele's), we can create a map/process flow of metabolic pathways that are dysregulated, and thereon find chemical compounds that are beneficial. 
3 snips I have are:
rs2242446 (CT)
rs3785143 (CT)
rs5568 (AC)

I am homozygous for the SLC6A2 Gene -Norepinephrine Transporter
POIS Free, 1+ yrs despite daily o's (with occasional pois episodes)
Pois symptoms: Peripheral (Skin: Urticaria, dryness, pale blotchy skin), Exasperation of: [Nerve weakness, Muscle weakness + Mental (CNS: Brain Fog, Irritation, Isolation, Speech lethargy, Anxiety)].
Other conditions: ASD, ADD, GA

Quantum

  • Administrator
  • Hero Member
  • *****
  • Posts: 1459
Re: Channelopathies
« Reply #6 on: July 23, 2021, 09:48:21 AM »
I have received my whole genome sequencing results, and I have found that I have at least one channelopathy ( I already suspected that I had it, but my genes confirmed it).
I may have another one, still analyzing my genome about this one...
However, I sure have a form of HypoKelemic Periodic Paralysis, type 1.  See my more detailed post at https://poiscenter.com/forums/index.php?topic=3694.msg41614#msg41614
You are 100% responsible for what you do with anything I post on this forum and of any consequence it could have for you.  Forum rule: ""Do not use POISCenter as a substitute for, or to give, medical advice" Read the remaining part at http://poiscenter.com/forums/index.php?topic=1.msg10259#msg10259

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #7 on: July 23, 2021, 12:56:14 PM »
I have found that I have at least one channelopathy...
https://en.wikipedia.org/wiki/Cav1.1
This could tie in with the decrease of cytokines post O, my suspicion of a decline of intracellular calcium via calcium channels. It's also associated with the ryanodine receptor RyR1 in skeletal muscle. Xanthines like caffeine activates RyR1. https://en.wikipedia.org/wiki/Ryanodine_receptor

I also have tension problems, as if it is unable to adept properly in certain situations. Had low urinary sodium once when POTS popped up. Hmm Dihydropyridine blocks Cav1.1. A cardiac ECG can point to channelopathies as well.
« Last Edit: July 23, 2021, 01:02:35 PM by Muon »

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #8 on: July 23, 2021, 07:11:06 PM »
Basically, I have loss of sensation on my penis glans and on the left side of my penis shaft. My brain was unable to receive hot and cold temperatures from the tip of my penis, on both sides of my penis glans, and on the left side of my penis shaft. The sensation issue on my penis glans and the left side of my penis shaft does not seem to go away, even with abstinence.
https://www.sciencedirect.com/science/article/abs/pii/S0091305713003389
In addition, it is postulated that mechano- and thermosensory activity of transient receptor potential (TRP) ion channels, located in skin receptors of the glans penis, are associated with lifelong PE.

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #9 on: July 24, 2021, 06:58:39 AM »
Calcium channels?

Something else, I had painfully stiff muscles due to POIS a week ago. The higher part of the back, shoulders and part of the upper arms were affected, the weird thing was it kept getting stiffer and stiffer up to the point I could barely move my right arm, it was that painful (there was only pain present during movement, not in rest). Moving my arm/shoulder, was like the feeling of almost tearing some muscles. I slept one night with clothes on because undressing was too painful. Quite a weird event, I have never experienced this intensity of stiffness before.

Bell's palsy = facial paralysis --> channelopathy?

IronFeather

  • Jr. Member
  • **
  • Posts: 60
Re: Channelopathies
« Reply #10 on: July 24, 2021, 08:49:19 AM »
Calcium channels?

Something else, I had painfully stiff muscles due to POIS a week ago. The higher part of the back, shoulders and part of the upper arms were affected, the weird thing was it kept getting stiffer and stiffer up to the point I could barely move my right arm, it was that painful (there was only pain present during movement, not in rest). Moving my arm/shoulder, was like the feeling of almost tearing some muscles. I slept one night with clothes on because undressing was too painful. Quite a weird event, I have never experienced this intensity of stiffness before.

Bell's palsy = facial paralysis --> channelopathy?

This is exactly what happened to me when my exercise intolerance appeared due to exposure to bleach. It had only happened once before, during a POIS episode too, and my neck was so stiff for two days that lifting my head up to take notes from the blackboard in class felt like I was ripping my neck muscles off. Then it happened three more times in March-April 2020 (twice in my right shoulder, once in my left elbow), and in May-June I already had both the exercise intolerance and the muscle shaking that have persisted ever since.

I believe channelopathies could be involved indeed. Maybe as a secondary cause, something that got damaged because of another imbalance or deficiency? I didn't have any of these symptoms before, they only appeared last year after the bleach, so I think it must be something else that is throwing everything out of balance. I know there's something going on with potassium in my case, as since this worsening happened I've had intense cravings of specific foods, that I could not explain, but later realized were all foods that are high on potassium (potatoes and bananas, mostly).

If I don't eat any of those during the day, I start getting a slight dizziness and my heart does all kinds of weird jolts and jumps. In fact, it's happening today. I first thought about potassium when Quantum commented this on my case summary thread:

I also have exercise intolerance.  When I do sports in the evening, I used to wake up the following night in hypotension and tachycardia.  Hopefully, I found that taking enough potassium ( around 16 mEq) and magnesium after sports spare me that awful discomfort.   However, it is not clear yet as to why potassium helps me, both in POIS and after exercise.
« Last Edit: July 24, 2021, 08:52:26 AM by IronFeather »
25-year-old Spanish woman with POIS symptoms for the last 12 years.
Suffering from exercise intolerance since April 2020.
My case thread, with medical tests results.

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #11 on: July 24, 2021, 01:19:38 PM »
https://forums.phoenixrising.me/threads/channelopathy-in-cfs.84906/

@Prospero
Discussion about TRMP3, progesterone, pregnenolone, mu-opioid interaction. NK cells contain this channel as well. My IL-2 drops down and wonder whether it suppresses NK cell function which could tie into nanna's theory about viral replication (it sure affects Tregs). I haven't read everything.

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #12 on: July 24, 2021, 01:29:30 PM »
I know there's something going on with potassium in my case, as since this worsening happened I've had intense cravings of specific foods, that I could not explain, but later realized were all foods that are high on potassium (potatoes and bananas, mostly).

Fox improved on banana's (potassium?). He had problems with swallowing food as a kid, this could indicate channelopathy.

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #13 on: July 24, 2021, 01:58:53 PM »
New POIS paper talking about a Piezo2 Channelopathy:
Post Orgasmic Illness Syndrome (POIS) and Delayed Onset Muscle Soreness (DOMS): Do They Have Anything in Common?
The piezo2 ion channel paper regarding premature ejaculation was already present under the PE header in the POIS paper archive thread.
« Last Edit: July 24, 2021, 02:06:09 PM by Muon »

Iwillbeatthis

  • Sr. Member
  • ****
  • Posts: 499
Re: Channelopathies
« Reply #14 on: July 24, 2021, 05:45:19 PM »
We should check for Voltage Gated Potassium Channel Complex Antibodies which are VGKC, LG1, and CASPR2 .

Gut bugs like H Pylori can really mess with mineral balance (especially potassium) and ion transport. So it's really important to treat these first if you do suspect any issues with potassium etc.

I found a high dose potassium electrolyte supplement (1000mg potassium) completely stopped my reactions to showers for a week, but in the end it ended up being too much potassium and I had the health crisis with my kidneys and stomach for month.

I have since developed suspected stomach ulcers (90% sure) from this health crisis: I found out afterwards that potassium supplements can cause holes in stomach, I also took two asprins in one night and was taking cell food mineral supplement that contains Deuterium sulfate. None of these in the doses should cause anyone ulcers but I think the combination of the three while having low secretory IGA caused an issue for me. It was specifically after the night of taking the two asprins when I started waking up with bad stomach pain.

All 3 of those things above gave me bad stomach pain and soreness and I started waking up with a very sore stomach every morning for a month but especially if I hadn't eaten dinner. And fats like butter would make the pain a lot worse.

I ended up healing the pain with Deglycyrrhizinated Licorice, probiotics, alka seltzer gold antacid (asprin free) and slippery elm powder. DGL and slippery elm coat and soothe the GI tract. The alka seltzer gold  (citric acid, potassium bicarbonate and sodium bicarbonate) was the most helpful for stopping the pain but I also noticed my autistic symptoms disappeared for two days and I could articulate and speak much better than normal. Too bad these effects on my autistic symptoms only lasted two days, then I started to feel very fatigued and had diarrhoea; potassium bicarbonate can bring gut bugs out of hiding and probably it was too much potassium for me.  After this happened I searched about alka seltzer gold and saw it is actually used as a treatment for autism and autoimmune diseases. I'll attach more info at the bottom. https://epiphanyasd.blogspot.com/2018/05/drinking-baking-soda-for-vagal-nerve.html

After he stomach ulcer pain had stopped and I was feeling good and healthy again, I thought I could try the potassium phosphate drops again just one drop in water 1% of the daily Value for potassium. Well this caused instant stomach pain ulcer symptoms came back, rashes on feet, red feet, bad anxiety, neuropathy and numbness in feet and hands which lasted weeks. This reaction alone seemed like the perfect example of a channelopathy. And my stomach became sensitive to meat. I healed it again with the same supplements, but now it the pain has come back again after trying antibacterials to kill salmonella infection.

Potassium balances the stomach PH, I see my urine PH jump from 5/6 acidic to 7 (alkaline) after taking the potassium, the change in PH levels could be the reason why I am getting all these symptoms from taking potassium. I tolerate the alka seltzer gold (potassium bicarbonate) much better than taking the potassium phosphate drops which cause awful symptoms. I also don't get any bad symptoms when taking a magnesium potassium krebs complex supplement so it could be the other electrolytes in the alka seltzer and the magnesium potassium krebs complex supplement which balance the potassium from causing issues.

I'm in a predicament I need to raise my potassium levels as they were very low, I also need to kill the infections like salmonella shown in my gut test but I can't do any of these until I have got rid of the ulcers for good. I am now considering buying a juicer and making cabbage juice as that seems to be the best remedy for ulcers after reading online. Conventional treatment for ulcers are  Proton pump inhibitors  but these can cause a whole host of further health problems. Even if I wanted these I wouldn't be able to get them as Uk healthcare has become a joke since Covid hit, and you need the stars to align if you want any help from these doctors with your health problems (I am specifically referring to the General Practitioners).

"We speculate that the anti-in?ammatory effects of oral NaHCO3 ingestion are mediated by activation of the cholinergic ant-in?ammatory pathway. The cholinergic anti-in?ammatory pathway has been reported to be the efferent arm of the anti-in?ammatory re?ex, which acts via vagal efferents to promote M2 macrophage polarization in the spleen and limit activation of the innate immune system, thereby preventing damage caused by excessive cytokine production. In?ammatory macrophages and excessive TNF-a production have been implicated in the pathology of a broad range of disease states, including rheumatoid arthritis, cardiovascular disease, atherosclerosis, irritable bowel disease, type 2 diabetes, and neurodegenerative diseases as well as others. Conversely, FOXP3+ Tregs have been shown to be bene?cial in a wide range of pathologies. FOXP3+ Tregs act to suppress activation of the immune system and induce immune tolerance. Evidence suggests that expansion of Tregs may be bene?cial in a wide variety of disease states that involve pathological activation of the immune system, including allergy, asthma, multiple sclerosis (29), graft versus host disease, diabetes, and hypertension as well as many others. Given its therapeutic potential against in?ammatory disease, there is currently much interest in methods to activate the cholinergic anti-in?ammatory pathway.”

"So is baking soda a panacea for auto-immune disease?
The big drawback of baking soda is that very often causes irritation to your digestion, but this should also apply to those indigestion tablets containing baking soda.
These tablets do not just contain sodium bicarbonate, they often contain potassium bicarbonate. It has been reported that the effect of drinking sodium bicarbonate will affect your blood electrolytes as follows
·        Raise sodium (and hence potentially blood pressure)

·        Raise calcium

·        Lower potassium

·        Raise bicarbonate

·        Lower chloride

In another study below in the use of baking soda in humans (table III in the full paper) the level of potassium fell 10%, from 4.3 to 3.9 mmol/l. Sodium did not change much at all.

So adding potassium bicarbonate is quite clever. It will naturally increase potassium but it has a negative effect on sodium.
Some DAN-type doctors use Alka Seltzer Gold, which contains
Anhydrous citric acid 1000 mg
Potassium bicarbonate 344 mg
Sodium bicarbonate  1050 mg
« Last Edit: July 24, 2021, 05:54:31 PM by Iwillbeatthis »

IronFeather

  • Jr. Member
  • **
  • Posts: 60
Re: Channelopathies
« Reply #15 on: July 25, 2021, 07:07:58 AM »
New POIS paper talking about a Piezo2 Channelopathy:
Post Orgasmic Illness Syndrome (POIS) and Delayed Onset Muscle Soreness (DOMS): Do They Have Anything in Common?
The piezo2 ion channel paper regarding premature ejaculation was already present under the PE header in the POIS paper archive thread.

I can't even believe some of the things they say in these papers. Do the researchers even read patients' stories?

"It is noteworthy that symptoms do not evolve in POIS patients during sexual activity in the absence of ejaculation".

Sigh. Anyway, they're not even explaining how this supposed "acute compression proprioceptive axonopathy" would have appeared in POIS patients. Are they saying we have a pre-existing injury? I remember reading someone's story in the forum saying he had some sort of nerve compression (it was Kit, I think) and that doctors suspected it was the cause of his POIS.
25-year-old Spanish woman with POIS symptoms for the last 12 years.
Suffering from exercise intolerance since April 2020.
My case thread, with medical tests results.

berlin1984

  • Global Moderator
  • Hero Member
  • *****
  • Posts: 571
  • Use Adaptogens and Antioxidants, they can help.
Re: Channelopathies
« Reply #16 on: July 25, 2021, 01:24:19 PM »
Fox improved on banana's (potassium?). He had problems with swallowing food as a kid, this could indicate channelopathy.

Quantum is also a fan.

1 x potassium citrate ( electrolytic rebalancing) ( IMPORTANT WARNING:  I personally have a tendency to low potassium , = hypokalemia. This is a personal condition, so, do not take potassium supplements without the advice of your health professional,  if you take too much of it for your own needs, it can be dangerous, and can even cause fatal cardiac arrhythmia )

berlin1984

  • Global Moderator
  • Hero Member
  • *****
  • Posts: 571
  • Use Adaptogens and Antioxidants, they can help.
Re: Channelopathies
« Reply #17 on: July 25, 2021, 01:35:01 PM »
I'm not a gene expert, so this is from my Promethease report when I search for "Piezo2"

rs12455924(C;C)
80.5%   Frequency (caucasian)

rs264272(C;C)
22.1%   Frequency (caucasian)

I have only the 23andme genome parts, not the full one.
No idea if this means anything, but I still post it here for further search reference.

berlin1984

  • Global Moderator
  • Hero Member
  • *****
  • Posts: 571
  • Use Adaptogens and Antioxidants, they can help.
Re: Channelopathies
« Reply #18 on: July 25, 2021, 01:38:46 PM »
Wow, I have a very long list of polymorphisms for the SCN5A gene (i.e. Nav 1.5 mutation you mention)
Just a few are:
rs1805124 (CC), 6% have
rs11710077 (TT), 2% have
rs12053903 (TT), 26% have
rs1805126 (AA), 28% have
rs11129795(GG), 68% have
rs6763048 (AA), 76% have

I only find those in my promethease:
rs12053903(T;T) 49.6%   Frequency
rs1805126(T;T) 47.8%   Frequency
rs6763048(A;A) 76.1%   Frequency
So from the three I find, we differ in rs1805126

EDIT: oh, i also find this one raw in my text file, we also differ there:
rs1805124   3   38645420   TT

Muon

  • Hero Member
  • *****
  • Posts: 2367
    • MCAD Thread
Re: Channelopathies
« Reply #19 on: July 25, 2021, 02:50:16 PM »
Do the researchers even read patients' stories?
I don't think so. Yes it was Kit I believe.