Transcript 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:
• 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 attackinducing situations
• Acetazolamide (Diamox)
Understanding
through Modeling…
During Attack
• Hospitalization
• Potassium
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 value
Tauh =.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.
600
500
APD (ms)
400
300
y = -4.1417x + 437.11
200
100
0
-20
-10
0
10
20
% change in [K]out
30
40
50
Sensitivity Analysis for Tau h
Sensitivity Analysis for tau h
60
y = 0.2583x + 40.5
Amplitude of AP (mV)
50
40
30
20
10
0
-60
-40
-20
0
(% ) change in Tau_h
20
40
60
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.
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
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