A major role for hERG in determining frequency of reentry in neonatal rat ventricular myocyte monolayer

Luqia Hou, Makarand Deo, Philip Furspan, Sandeep V. Pandit, Sergey Mironov, David S. Auerbach, Qiuming Gong, Zhengfeng Zhou, Omer Berenfeld, José Jalife

    Research output: Contribution to journalArticlepeer-review

    42 Scopus citations


    Rationale: The rapid delayed rectifier potassium current, IKr, which flows through the human ether-a-go-go-related (hERG) channel, is a major determinant of the shape and duration of the human cardiac action potential (APD). However, it is unknown whether the time dependency of IKr enables it to control APD, conduction velocity (CV), and wavelength (WL) at the exceedingly high activation frequencies that are relevant to cardiac reentry and fibrillation. Objective: To test the hypothesis that upregulation of hERG increases functional reentry frequency and contributes to its stability. Methods and results: Using optical mapping, we investigated the effects of IKr upregulation on reentry frequency, APD, CV, and WL in neonatal rat ventricular myocyte (NRVM) monolayers infected with GFP (control), hERG (IKr), or dominant negative mutant hERG G628S. Reentry frequency was higher in the IKr-infected monolayers (21.12±0.8 Hz; n=43 versus 9.21±0.58 Hz; n=16; P<0.001) but slightly reduced in G628S-infected monolayers. APD80 in the IKr-infected monolayers was shorter (>50%) than control during pacing at 1 to 5 Hz. CV was similar in both groups at low frequency pacing. In contrast, during high-frequency reentry, the CV measured at varying distances from the center of rotation was significantly faster in IKr-infected monolayers than controls. Simulations using a modified NRVM model predicted that rotor acceleration was attributable, in part, to a transient hyperpolarization immediately following the AP. The transient hyperpolarization was confirmed experimentally. Conclusions: hERG overexpression dramatically accelerates reentry frequency in NRVM monolayers. Both APD and WL shortening, together with transient hyperpolarization, underlies the increased rotor frequency and stability.

    Original languageEnglish (US)
    Pages (from-to)1503-1511
    Number of pages9
    JournalCirculation research
    Issue number12
    StatePublished - Dec 10 2010


    • delayed rectifier potassium channel
    • hERG
    • optical mapping
    • reentry
    • ventricular fibrillation

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine


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