The myotonias are of special interest in CFS because some people purported to have CFS have turned out to have a myotonia instead (Graves and Hanna 2005). They occur when overly excitable muscle membranes respond to a single nerve impulse with multiple contractions.
Graves and Hanna state myotonias should be considered in anyone who complains of muscle stiffness. Although these diseases are genetically based the symptoms they evoke sometimes do not occur until maturity. In Thomsen’s disease, a chloride channel dysfunction causes constant or intermittent muscle stiffness that is relieved during exercise (the warm up phenomena).
A sodium channel dysfunction in paradoxical myotonia results in muscle stiffness that increases during exercise and can be precipitated by low temperatures. Testing for some of these diseases involves measurements taken in the post- exercise period – obviously a key period in CFS as well (Graves and Hanna 2005).
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Speculation
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.
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Evidence of a Channelopathy in CFS
Some indirect evidence of ion channel disruption is provided by Chaudhuri et al’s finding of increased resting energy expenditure (REE) in CFS patients. Since about 25% of the energy expended during resting goes to maintaining ion gradients in the cell, the authors speculate the increased REE seen in CFS could be due to compensation for faulty ion channel functioning.
CFS patients also appear to be particularly susceptible to some substances (alcohol, anesthesia, some cholesterol lowering drugs) known to effect either membrane integrity (alcohol) and/or ion function (anesthethetics). Indeed fatigue is a common symptom of a new anti-epileptic drug, dezinamide, targeting sodium channels.
Results from a thallium scan of the cardiac muscle in CFS patients suggest a potassium ion channel dysfunction that may be responsible for the cardiomyopathy reported by Lerner and now advocated by Cheney. Chaudhuri and Behan believe a potassium channelopathy is mostly likely to occur in CFS.
Potential causes of channel dysfunction – The natural history of CFS suggests that an early pathogenic or toxic insult often occurs. Several viruses, including HIV and the picornaviruses are able to alter ion channel flow. Herpesviruses have also been linked, interestingly enough given their history in CFS, to altered ion channel functioning.
Ciguatoxin, a neuronal sodium channel disruptor, produces many symptoms, including fatigue, similar to those that occur in CFS. Studies indicate a substantial number of CFS patients have extremely high levels of the ciguatera epitope. (Hokama et al. 2002, 2003a/b). Toxic insults from organophosphates, lead, insecticides, pesticides can also alter ion channel activity.
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*Update – Since this paper was published in 1999 channelopathies have become a more prominent research topic in CFS.
Ciguatoxin
Greatly increased levels of the ciguatoxin epitope, a marker of altered sodium channel activity, in most CFS patients provide the best evidence yet a (sodium) channelopathy occurs in CFS. Whether these findings reflect a chronic disease process or something more specific to CFS is unclear but research, thankfully, is underway to elucidate the intersection between CFS and ciguatera (Pearn 2001, Hokama et .al. 2002, 2003a/b).
RNase L
The breakup of the RNase L enzyme releases fragments that appear able to interact with the ABC transporters that control the flow of ions in and out of the cell (Englebienne et. al. 2001, Nijs et. al 2004). De Meirleir et. al. did not, however, find strong evidence of systemic channelopathy in CFS (see
Patrick Englebienne’s review). Reports from the 2004 AACFS conference indicate, however, that RNase L fragmentation affects the ability of the multi-drug resistant transporter to remove toxins from the cell.
Gene microarray studies
Perhaps most intriguing of all a recent study found that genes involved in ion channel functioning were among those most prominently altered between CFS patients and controls both prior to and after exercise (Whistler et. al. 2005
I don’t know who wrote it? I’m interested more in the general hypothesis rather than a specific paper. It seemed like it was discussed quite a bit at one point then hasn’t been for a few years. Was this because evidence was found to refute the idea of channelopathy in ME, or was it simply lack of funding?