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Hypokalemic Periodic Paralysis II BME 301 Spring 2008 Dr. Entcheva Group 6
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Hypokalemic Periodic Paralysis II: Symptoms Weakness Paralysis Temporal duration: Up to 24 hours
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Hypokalemic Periodic Paralysis II: Factors Mutation of SCN4A gene Situational: Excess of carbohydrates, salt, alcohol Immediate rest after strenuous activity Sudden temperature change
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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. *
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Hypokalemic Periodic Paralysis II: Treatment Preventative Diet low in Na and carbohydrates Avoidance of attack- inducing situations Acetazolamide (Diamox) During Attack Hospitalization Potassium Understanding through Modeling…
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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
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Hypokalemic Periodic Paralysis II: GUI
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Hypokalemic Periodic Paralysis II: Code Changes
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Two changes: K O & τ h
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Change in [K]out
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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
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Hypokalemic Periodic Paralysis II: Sodium Gate *Taken from Dr. Entcheva’s BME 301 Spring 2008 in-class lecture.
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Sensitivity analysis for [K]out
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Sensitivity analysis [K]out cont.
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Sensitivity Analysis for Tau h
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Sensitivity Analysis for tau h
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HypoPP2 affects Skeletal Muscle NOT 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.
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Hypokalemic Periodic Paralysis II: Diseased Cardiac Ventricular Cell Simulation HypoPP2 Normal Cell
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Hypokalemic Periodic Paralysis II: Skeletal Muscle Cell Simulation
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Hypokalemic Periodic Paralysis II: Treatment of Cardiac Ventricular Cell Simulation
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References 1. Mosenkis, Ari. Hypokalemic periodic paralysis. U.S. National Library of Medicine. 01 March 2006.. 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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