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- W2008471566 abstract "Gap junction redistribution and reduced expression, a phenomenon termed gap junction remodeling (GJR), is often seen in diseased hearts and may predispose toward arrhythmias. We have recently shown that short-term pacing in the mouse is associated with changes in connexin43 (Cx43) expression and localization but not with increased inducibility into sustained arrhythmias. We hypothesized that short-term pacing, if imposed on murine hearts with decreased Cx43 abundance, could serve as a model for evaluating the electrophysiological effects of GJR. We paced wild-type (normal Cx43 abundance) and heterozygous Cx43 knockout (Cx43 +/− ; 66% mean reduction in Cx43) mice for 6 h at 10–15% above their average sinus rate. We investigated the electrophysiological effects of pacing on the whole animal using programmed electrical stimulation and in isolated ventricular myocytes with patch-clamp studies. Cx43 +/− myocytes had significantly shorter action potential durations (APD) and increased steady-state ( I ss ) and inward rectifier ( I K1 ) potassium currents compared with those of wild-type littermate cells. In Cx43 +/− hearts, pacing resulted in a significant prolongation of ventricular effective refractory period and APD and significant diminution of I ss compared with unpaced Cx43 +/− hearts. However, these changes were not seen in paced wild-type mice. These data suggest that Cx43 abundance plays a critical role in regulating currents involved in myocardial repolarization and their response to pacing. Our study may aid in understanding how dyssynchronous activation of diseased, Cx43-deficient myocardial tissue can lead to electrophysiological changes, which may contribute to the worsened prognosis often associated with pacing in the failing heart." @default.
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- W2008471566 date "2008-11-01" @default.
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- W2008471566 title "Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents" @default.
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- W2008471566 doi "https://doi.org/10.1152/ajpheart.590.2008" @default.
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