Nicotine Induces a Long QT Phenotype in Kcnq1-Deficient Mouse Hearts

Abstract

We have previously shown that targeted disruption of the mouse Kcnq1 gene produces a long QT phenotype in vivo that requires extracardiac factors for manifestation (Casimiro et al., 2001). In the present study, we explore the hypothesis that autonomic neuroeffector transmission represents the "extracardiac" stimulus that induces a long QT phenotype in mouse hearts lacking Kcnq1. Using the isolated perfused (Langendorff) mouse heart preparation, we challenged wild-type (Kcnq1 ϩ/ϩ ) and mutant (Kcnq1 Ϫ/Ϫ ) mouse hearts with nicotine, an autonomic stimulant. ECGs were recorded continuously, and QT intervals were compared at baseline and peak nicotineinduced heart rates. No significant differences in QT or any other ECG parameters were observed in Kcnq1 ϩ/ϩ versus Kcnq1 Ϫ/Ϫ hearts at baseline. In the presence of nicotine, however, the JT, QT, and rate-corrected QT (QTc) intervals were significantly prolonged in Kcnq1 Ϫ/Ϫ hearts relative to Kcnq1

Subcellular localization of the delayed rectifier K+channels KCNQ1 and ERG1 in the rat heart

“…However, because KCNQ1 is capable of interaction with all other members of the KCNE family, it can be speculated that KCNQ1 contributes to other K ϩ currents than I Ks in rat myocytes. In support of our data, a role for KCNQ1 in the mouse heart has recently been suggested in relation to sympathetic stimulation (53). In KCNQ1-targeted deletion mice, long QT phenotypes were observed in response to sympathetic stimulation indicating a role for KCNQ1 in cardiac repolarization in the presence of catecholamines.…”

Loss of type 9 adenylyl cyclase triggers reduced phosphorylation of Hsp20 and diastolic dysfunction

“…We do not detect endogenous KCNQ1 from heart lysates or by immunoprecipitation of Yotiao or KCNQ1 4 . Moreover, knockout of KCNQ1 does not alter heart rate or QT interval at baseline, although these features are prolonged when challenged with nicotine 35 . Thus it is unclear if the bradycardia in AC9 −/− is due to decreased phosphorylation of KCNQ1 or another, yet identified, Yotiao-associated K + channel in mouse sinoatrial node.…”

WTC deafness Kyoto (dfk): a rat model for extensive investigations ofKcnq1functions

“…They displayed abnormal T-wave form and prolongation of the QT interval when measured in vivo, but not in isolated hearts (5). In addition, nicotine challenge of the isolated heart and acute stress due to saline injection in vivo revealed that sympathetic stimulation induced a long-QT phenotype in Kcnq1-deficient mice (28).…”