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Hypokalemic Periodic Paralysis II

Hypokalemic Periodic Paralysis II. BME 301 Spring 2008 Dr. Entcheva Group 6. Hypokalemic Periodic Paralysis II: Symptoms. Weakness Paralysis . Temporal duration: Up to 24 hours. Hypokalemic Periodic Paralysis II: Factors. Mutation of SCN4A gene Situational:

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Hypokalemic Periodic Paralysis II

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  1. Hypokalemic Periodic Paralysis II BME 301 Spring 2008 Dr. Entcheva Group 6

  2. Hypokalemic Periodic Paralysis II: Symptoms Weakness Paralysis Temporal duration: Up to 24 hours

  3. Hypokalemic Periodic Paralysis II: Factors Mutation of SCN4A gene Situational: • Excess of carbohydrates, salt, alcohol • Immediate rest after strenuous activity • Sudden temperature change

  4. Hypokalemic Periodic Paralysis II: Action Potential * *Jurkat-Rott, Karin, et al. Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. PNAS. 2000 Aug; 97(17):9549-54.

  5. Hypokalemic Periodic Paralysis II: Treatment Preventative During Attack Hospitalization Potassium • Diet low in Na and carbohydrates • Avoidance of attack-inducing situations • Acetazolamide (Diamox) Understanding through Modeling…

  6. Hypokalemic Periodic Paralysis II: Modeling Model of diseased cell’s electrical activity using Matlab • Creation of Graphical User Interface (GUI) • Changes to code supplied by Dr. Entcheva

  7. Hypokalemic Periodic Paralysis II: GUI

  8. Hypokalemic Periodic Paralysis II: Code Changes

  9. Two changes: KO&τh Hypokalemic Periodic Paralysis II: Code Changes

  10. Change in [K]out

  11. Changes to Tau h Tau_h in HypoPP is about 65% of the normal value Tauh =.65 No changes to Tau_m or Tau_j values  Tauj = Taum = 1

  12. Hypokalemic Periodic Paralysis II: Sodium Gate *Taken from Dr. Entcheva’s BME 301 Spring 2008 in-class lecture.

  13. Sensitivity analysis for [K]out

  14. Sensitivity analysis [K]out cont.

  15. Sensitivity Analysis for Tau h

  16. Sensitivity Analysis for tau h

  17. HypoPP2 affects Skeletal MuscleNOT CARDIAC MUSCLE!! *Jurkat-Rott, Karin, et al. Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. PNAS. 2000 Aug; 97(17):9549-54.

  18. Hypokalemic Periodic Paralysis II: Diseased CardiacVentricular CellSimulation HypoPP2 Normal Cell

  19. Hypokalemic Periodic Paralysis II: SkeletalMuscle CellSimulation

  20. Hypokalemic Periodic Paralysis II: Treatment of Cardiac Ventricular CellSimulation

  21. References 1. Mosenkis, Ari. Hypokalemic periodic paralysis. U.S. National Library of Medicine. 01 March 2006. <http://www.nlm.nih.gov/medlineplus/ency/article/000312.htm>. 2. Sternberg, Damien, Thierry Maisonobe, and Karin Jurkat-Rott. "Hypokalaemic Periodic Paralysis Type 2 Caused by Mutations At Codon 672 in the Muscle Sodium Channel Gene SCN4A." Brain: a Journal of Neurology 124 (2001): 1091-1099. PubMed. 21 Mar. 2008. 3. Jurkat-Rott, Karin, et al. “Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.” PNAS. 2000 Aug; 97(17):9549-54. 4. Bulman DE, Scoggan KA, van Oene MD, Nicolle MW, Hahn AF, Tollar LL, et al. A novel sodium channel mutation in a family with hypokalemic periodic paralysis. Neurology 1999; 53: 1932–6. 5. Sansone, V et al. Treatment for periodic paralysis. Cochrane Database Syst Rev. 2008 Jan 23;(1) 6. Hypokalemic Periodic Paralysis: A Model for a Clinical and Research Approach to a Rare Disorder.  Neurotherapeutics, Volume 4, Issue 2, Pages 225-232 B. Fontaine, E. Fournier, D. Sternberg, S. Vicart, N. Tabti

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