Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism.

ABSTRACT:

Background

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.

Methods and results

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.

SUBMITTER: Clancy CE 

PROVIDER: S-EPMC1997279 | biostudies-literature | 2002 Mar

REPOSITORIES: biostudies-literature