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

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Presentation on theme: "Hypokalemic Periodic Paralysis II BME 301 Spring 2008 Dr. Entcheva Group 6."— Presentation transcript:

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 Aug; 97(17): *

5 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…

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: K O & τ h

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 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 Aug; 97(17):

18 Hypokalemic Periodic Paralysis II: Diseased Cardiac Ventricular Cell Simulation HypoPP2 Normal Cell

19 Hypokalemic Periodic Paralysis II: Skeletal Muscle Cell Simulation

20 Hypokalemic Periodic Paralysis II: Treatment of Cardiac Ventricular Cell Simulation

21 References 1. Mosenkis, Ari. Hypokalemic periodic paralysis. U.S. National Library of Medicine. 01 March 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): PubMed. 21 Mar Jurkat-Rott, Karin, et al. “Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.” PNAS Aug; 97(17): 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 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 B. Fontaine, E. Fournier, D. Sternberg, S. Vicart, N. Tabti


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