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Dipeptidyl aminopeptidase–like protein 6 regulates the INa-Ito balance influencing cardiac electrophysiology and arrhythmogenesis
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DOI：10.1126/scitranslmed.adn3180.png)
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Abstract
En 中文
Genetic variants of dipeptidyl aminopeptidase–like protein 6 (DPP6) have been linked to cardiac arrhythmias, but the role of DPP6 in regulating Kv4 channel–mediated cardiac transient-outward current (Ito) and Nav1.5-mediated cardiac sodium current (INa) is not fully understood. In heterologous in vitro systems and human induced pluripotent stem cell–derived cardiomyocytes, Rossetti et al. found that DPP6 variants linked to long-QT syndrome and J-wave syndromes (JWSs) led to hypo- and hyperinhibition of INa, respectively. Ito was decreased by the long-QT variants and increased by the JWS variants when coexpressed with Purkinje cell Ito subunits. In silico modeling of INa and Ito supported these observations, and electrocardiographic imaging in individuals with DPP6 variants also supported these biological observations. Together, these data show how DPP6 is important for regulating the opposing activities of INa and Ito in cardiac arrhythmogenesis. —Brandon Berry
Keywords:
DPP6
INa
Ito
cardiac arrhythmias
electrophysiology
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