NEW ELECTROPHYSIOLOGICAL INSIGHTS INTO AN SCN5A MUTATION CAUSING LQT
The D1790G mutation in the C-terminus of SCN5A gene §causes long-QT syndrome (LQT). Flecainide was shown §to normalize the QT-interval of D1790G patients. In §contrast, lidocaine, which shortens QTc in LQT3 §patients who are carriers of KPQ mutation, is §ineffective in treating D1790G patients. These §observations imply that the mechanism of QT §prolongation in D1790G carriers is different. §Over the last years different expression models §showed conflicting results in trying to explain the §QT prolongation in carriers of this mutation. §Furthermore, it is now well established that ion §channels, including Na+ channels, can be regulated §by G protein subunits.§In an attempt to clarify the underlying mechanism, §this work characterized the mutation §electrophysiologically in frog oocytes and §investigated both the involvement of G protein §subunits and the effects of different medications on §the mutant channel.§Basic researchers and cardiologists may find that §this analysis helps to shed some light on the §structure-function relationship of the human sodium §channel, and that it can pave the way for a §therapeutic rationale for the patients.