Periodic paralysis, hypokalemic

Mutation of the human Cavl.l gene is associated with hypokalemic periodic paralysis. Deletion of the Cav1.3 gene leads to viable pups that are deaf and have cardiac arrhythmia at rest. Mutation of the human Cavl. 4 gene is associated with X-linked congenital stationary night blindness. 

A fall in serum is commonly associated with hypokalemic periodic paralysis. Primary hypokalemic paralysis is usually first expressed in children and young adults. Paralytic attacks may fluctuate with remarkable frequency, and there is a common diurnal variation in severity, with weakness especially bad in the morning and evening. The condition has an autosomal dominant pattern of inheritance caused by an abnormality in or close to locus lql3. The gene product is unknown. 

The major mineralocorticoid, aldosterone, is secreted by cells of the zona glomerulosa. Primary hyperaldosteronism (Conn s syndrome) is associated with potassium depletion which is, in mm, responsible for the observed neuromuscular abnormalities seen in the disorder. These are similar to those seen in hypokalemic periodic paralysis (PP), with episodic and severe exacerbations of fixed muscle weakness. Muscle biopsy shows occasional muscle necrosis and vacuoles often these feamres are accompanied by mbular aggregates as in hypokalemic PP. All these changes can be attributed to the hypokalemia and not to excess aldosterone production per se. 

Hypokalemic periodic paralysis (MIM 114208) Slow Ca" voltage channel (DHPR) Skeletal muscle... 

Hypokalemic periodic paralysis is due to calcium channel mutations 721... 

Ptacek, L., Tawil, R., Griggs, R. et al. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 77 863-898,1994. 

Carbonic anhydrase inhibitors have been used as adjuvants in the treatment of epilepsy and in some forms of hypokalemic periodic paralysis and to increase urinary phosphate excretion during severe hyperphosphatemia. 

Table 4. CACNA1S (Cavl.l, als) Functional results for mutations associated with HypoPP = Hypokalemic periodic paralysis and MHS = Malignant hyperthermia susceptibility (only those HypoPP mutations with functional data are listed)...

Jurkat-Rott K, Mitrovic N, Hang C, Kouzmekine A, Iaizzo P, Herzog J, Lerche H, Nicole S, Vale-Santos J, Chauveau D, Fontaine B, Lehmann-Horn F (2000b) Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc Natl Acad Sci U S A 97 9549-9554. 

Morrill JA, Brown RH, Jr., Cannon SC (1998) Gating of the L-type Ca channel in human skeletal myotubes an activation defect caused by the hypokalemic periodic paralysis mutation R528H. J Neurosci 18 10320-10334. 

Rudel R, Lehmann-Horn F, Ricker K, Kuther G (1984) Hypokalemic periodic paralysis in vitro investigation of muscle fiber membrane parameters. Muscle Nerve 7 110-120. 

Ruff RL (2000) Skeletal muscle sodium current is reduced in hypokalemic periodic paralysis. Proc Natl Acad Sci U S A 97 9832-9833. 

Tricarico D, Servidei S, Tonali P, Jurkat-Rott K, Camerino DC (1999) Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis. J Clin Invest 103 675-682. 

Calcium channel CACNAIS lq31-32 Cavl.l Hypokalemic periodic paralysis 1 D Unclear... 

Carle T, Lhuillier L, Luce S, Sternberg D, Devuyst O, Fontaine B, Tabti N. Gating defects of a novel Na+channel mutant causing hypokalemic periodic paralysis. Biochem. Biophys. Res. Commun. 2006 348 653-661. 

Struyk AF, Cannon SC. A Na+Channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. J. Gen. Physiol. 2007 130 11-20. 

Jurkat-Rott K, Lehmann-Horn F. Do hyperpolarization-induced proton currents contribute to the pathogenesis of hypokalemic periodic paralysis, a voltage sensor channelopathy J. Gen. Physiol. 2007 130 1-5. 

Ikeda K, Iwasaki Y, Kinoshita M, Yabuki D, Igarashi O, Ichikawa Y, Satoyoshi E. Acetazolamide-induced muscle weakness in hypokalemic periodic paralysis. Intern Med 2002 41(9) 743-5. 

Adenylate kinase, which is abundant in muscle as in many other tissues, decreases in dystrophic mouse and human muscle (H6, P7). This enzyme, by interconverting adenine nucleotides, probably functions in the control of glycolysis it seems reasonable to suppose, therefore, that its activity may be governed by the same factors which influence glycolytic enzymes, as discussed above. A severe decline in the activity of AMP deaminase occurs in muscular dystrophy (P6, P7) and also in denervated muscle (M12) and in some cases of muscle affected by hypokalemic periodic paralysis (E6). Skeletal muscle normally contains a higher concentration of this enzyme than other tissues in fact, it is almost absent from some, such as liver. Its physiological function, and hence the significance of the sharp decline in its activity in diseased muscle, is still a matter of speculation. 

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