Markovian model for cardiac sodium channel (Clancy, Rudy 2002)

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Accession:62661
Complex physiological interactions determine the functional consequences of gene abnormalities and make mechanistic interpretation of phenotypes extremely difficult. A recent example is a single mutation in the C terminus of the cardiac Na(+) channel, 1795insD. The mutation causes two distinct clinical syndromes, long QT (LQT) and Brugada, leading to life-threatening cardiac arrhythmias. Coexistence of these syndromes is seemingly paradoxical; LQT is associated with enhanced Na(+) channel function, and Brugada with reduced function. Using a computational approach, we demonstrate that the 1795insD mutation exerts variable effects depending on the myocardial substrate. We develop Markov models of the wild-type and 1795insD cardiac Na(+) channels. See reference for more and details. The model files were submitted by: Dr. Jiun-Shian Wu, Dr. Sheng-Nan Wu, Dr. Ruey J. Sung, Han-Dong Chang.
Reference:
1 . Clancy CE, Rudy Y (2002) Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 105:1208-13 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I Sodium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: XPP;
Model Concept(s): Ion Channel Kinetics; Pathophysiology; Heart disease; Brugada; Long-QT;
Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]; Chang, Han-Dong; Wu, Jiun-Shian [coolneon at gmail.com]; Sung, Ruey J ;
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Ina_Markov
                            

Clancy CE, Rudy Y (2002) Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 105:1208-13[PubMed]

References and models cited by this paper

References and models that cite this paper

Abriel H, Cabo C, Wehrens XH, Rivolta I, Motoike HK, Memmi M, Napolitano C, Priori SG, Kass R (2001) Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the cardiac Na(+) channel. Circ Res 88:740-5

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Chandra R, Starmer CF, Grant AO (1998) Multiple effects of KPQ deletion mutation on gating of human cardiac Na+ channels expressed in mammalian cells. Am J Physiol 274:H1643-54 [PubMed]

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(27 refs)