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.
Model Type: Channel/Receptor
Currents: I Sodium
Model Concept(s): Ion Channel Kinetics; Pathophysiology; Heart disease; Brugada; Long-QT; Markov-type model
Simulation Environment: XPPAUT
Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]; Chang, Han-Dong; Wu, Jiun-Shian [coolneon at gmail.com]; Sung, Ruey J
References:
Clancy CE, Rudy Y. (2002). Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation. 105 [PubMed]