Hypokalemic Periodic Paralysis II

BME 301 Spring 2008Dr. 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:• Excess of carbohydrates, salt, alcohol• Immediate rest after strenuous activity• Sudden temperature change

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.

*

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…

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

Hypokalemic Periodic Paralysis II: GUI

Hypokalemic Periodic Paralysis II: Code Changes

Hypokalemic Periodic Paralysis II: Code Changes

Two changes:

KO & τh

Change in [K]out

Changes to Tau h

Tau_h in HypoPP is about 65% of the normal valueTauh =.65 No changes to Tau_m or Tau_j values Tauj = Taum = 1

Hypokalemic Periodic Paralysis II: Sodium Gate

*Taken from Dr. Entcheva’s BME 301 Spring 2008 in-class lecture.

Sensitivity analysis for [K]out

Sensitivity analysis [K]out cont.

y = -4.1417x + 437.11

0

100

200

300

400

500

600

-20 -10 0 10 20 30 40 50

% change in [K]out

AP

D (

ms

)

Sensitivity Analysis for Tau h

Sensitivity Analysis for tau h

y = 0.2583x + 40.5

0

10

20

30

40

50

60

-60 -40 -20 0 20 40 60

(%) change in Tau_h

Am

plit

ud

e o

f A

P (

mV

)

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.

Hypokalemic Periodic Paralysis II: Diseased Cardiac Ventricular Cell Simulation

HypoPP2

Normal Cell

Hypokalemic Periodic Paralysis II: Skeletal Muscle Cell Simulation

Hypokalemic Periodic Paralysis II: Treatment of Cardiac Ventricular Cell Simulation

References1. 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