Po-676-01 a versatile chemical-genetic approach to determine bases for arrhythmogenesis and sodium channelopathies

The voltage gated sodium channel NaV1.5 controls cardiac excitability and is an established therapeutic target; mutations in the Scn5a gene, which encodes NaV1.5, are associated with inherited arrhythmia syndromes such as Brugada and Long-QT. Other NaV isoforms, especially NaV1.1 and 1.8, have been strongly implicated in cardiac rhythmogenesis, however their presence in cardiomyocytes and functional roles are unresolved and contentious. Direct observation of non-NaV1.5 isoform currents would serve to address this outstanding question on a fundamental level, however the inability to selectively and completely silence NaV1.5 has prevented such a study.