Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes

Familial long QT syndrome (LQTS) and Brugada syndrome are two distinct huma n hereditary cardiac diseases known to cause ventricular tachyarrhythmias ( torsade de pointes) and idiopathic ventricular fibrillation, respectively, which can both lead to sudden death. Objective: In this study we have ident ified and electrophysiologically characterized, in patients having either L QTS or Brugada syndrome, three mutations in SCN5A (a cardiac sodium channel gene). Method: The mutant channels were expressed in a mammalian expressio n system and studied by means of the patch clamp technique. Results: The R1 512W mutation found in our first patient diagnosed with Brugada syndrome pr oduced a slowing of both inactivation and recovery from inactivation. The R 4132G mutation found in our second patient who also presented Brugada syndr ome, resulted in no measurable sodium currents. Both Brugada syndrome patie nts showed ST segment elevation and right bundle-branch block, and had expe rienced syncopes. The E1784K mutation found in the LQTS showed a persistent inward sodium current, a hyperpolarized shift of the steady-sate inactivat ion and a faster recovery from inactivation. Conclusion: The different clin ical manifestations of these three mutations most probably originate from t he distinct electrophysiological abnormalities of the mutant cardiac sodium channels reported in this study. (C) 2000 Elsevier Science BN. All rights reserved.