hERG overexpression significantly increased reentry frequency in neonatal rat ventricular myocyte monolayers compared to control (21.12 vs 9.21 Hz; P<0.001).
Does hERG overexpression increase functional reentry frequency and contribute to its stability in neonatal rat ventricular myocyte monolayers?
Overexpression of hERG in neonatal rat ventricular myocyte monolayers dramatically accelerates reentry frequency and stability due to APD and wavelength shortening along with transient hyperpolarization.
Absolute Event Rate: 21.12% vs 9.21%
p-value: p=<0.001
RATIONALE: the rapid delayed rectifier potassium current, I(Kr), 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 I(Kr) 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 I(Kr) upregulation on reentry frequency, APD, CV, and WL in neonatal rat ventricular myocyte (NRVM) monolayers infected with GFP (control), hERG (I(Kr)), or dominant negative mutant hERG G628S. Reentry frequency was higher in the I(Kr)-infected monolayers (21.12 ± 0.8 Hz; n=43 versus 9.21 ± 0.58 Hz; n=16; P50%) 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 I(Kr)-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.
Hou et al. (Fri,) conducted a other in Cardiac reentry and fibrillation (in vitro model) (n=59). hERG (I(Kr)) overexpression vs. GFP (control) or dominant negative mutant hERG G628S was evaluated on Reentry frequency (p=<0.001). hERG overexpression significantly increased reentry frequency in neonatal rat ventricular myocyte monolayers compared to control (21.12 vs 9.21 Hz; P<0.001).