[Recent progress on the searchs of pathogenesis of thyrotoxic periodic paralysis].
In Japan, more than 60% of hypokalemic periodic paralysis is thyrotoxic instead of familial type frequently experienced in Caucasian countries. The pathogenesis of familial hypokalemic periodic paralysis (FHPP) has been elucidated to be due to the mutation of one of the genes in either Ca(CACN1AS), Na(SCN4A) or K channel(KCNE3). Clinical features of thyrotoxic periodic paralysis (TPP) is very similar to that of FHPP and rigorous attempts have been devoted to the search of the gene mutation of ion channels in TPP. To date, however, no such an attempt has been successful except for the findings of SNiPs in those ion channel genes or in the vicinity of TRE of CACN1AS. Those SNiPs may provide a risk to the attack of TPP. In TPP, we and others reported that the serum insulin level tremendously elevated prior to the attack of paralysis. There were clinical evidences indicating that hypokalemic periodic paralysis is caused by the depolarization block of muscle cell membrane instead of hyperpolarization block once assumed previously. Otsuka reported that insulin can induce depolarization block of muscle membrane in low K concentration by increasing membrane permeability to Na. We have reported that K deficiency and thyroid hormone excess increased NaK-ATPase and may sensitize the muscle membrane to the effect of insulin to cause depolarization in an animal model. In fact, in Japan, incidence of TPP of male decreased from 8.6% in 1958 to 4.3% in 1998. During this 40 years, intake of K was increased from 43 to 65 mEq per day per person as described by the National Survey of Nutrition. The SNiPs of ion channel genes, together with K deficiency or thyroid hormone excess, may provide a risk to the occurrence of TPP.
Shishiba
Yoshiaki
Y
Kimitsu Hospital.
D000818:Animals; D005260:Female; D006801:Humans; D007328:Insulin; D007473:Ion Channels / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation; D010243:Paralysis / Q000453:epidemiology / Q000209:etiology*; D010507:Periodicity; D020641:Polymorphism, Single Nucleotide; D011191:Potassium Deficiency / Q000150:complications; D044469:Racial Groups; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013971:Thyrotoxicosis / Q000453:epidemiology / Q000209:etiology*
D007328:Insulin; D007473:Ion Channels; D000254:Sodium-Potassium-Exchanging ATPase