hypokalemic periodic paralysis ii bme 301 spring 2008 dr. entcheva group 6
TRANSCRIPT
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Hypokalemic Periodic Paralysis II
BME 301 Spring 2008Dr. 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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Hypokalemic Periodic Paralysis II: Code Changes
Two changes:
KO & τh
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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 valueTauh =.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.
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
)
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Sensitivity Analysis for Tau h
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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
)
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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.
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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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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