Sex hormonal regulation of cardiac ion channels in drug-induced QT syndromes.
Female sex is an independent risk factor for development of torsade de pointes (TdP) arrhythmias not only in congenital long QT syndromes but also in acquired long QT syndromes. Clinical and experimental evidences suggest that the gender differences may be due to, at least in part, gender differences in regulation of rate-corrected QT (QTC) interval between men and women. In adult women, both QTCinterval and arrhythmic risks in TdP alter cyclically during menstrual cycle, suggesting a critical role of female sex hormones in cardiac repolarization process. These gender differences in fundamental cardiac electrophysiology result from variable ion channel expression and diverse sex hormonal regulation via long term genomic and acute non-genomic actions, and sex differences in drug responses and metabolisms. In particular, non-genomic actions of testosterone and progesterone on cardiac ion channels are likely to contribute to the gender differences in cardiac repolarization processes. This review summarizes current knowledge on sex hormonal regulation of cardiac ion channels which contribute to cardiac repolarization processes and its implication for gender differences in drug-induced long QT syndromes.
Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. Electronic address: junkokuro.bip@mri.tmd.ac.jp.
Junko
J
Kurokawa
Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Masami
M
Kodama
Department of Pharmacology, University of California, Davis, Davis, CA, United States.
Colleen E
CE
Clancy
Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Tetsushi
T
Furukawa
D000818:Animals; D005260:Female; D023281:Genomics; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008597:Menstrual Cycle / Q000502:physiology; D011374:Progesterone / Q000378:metabolism; D012307:Risk Factors; D012737:Sex Factors; D013739:Testosterone / Q000378:metabolism; D016171:Torsades de Pointes / Q000209:etiology / Q000503:physiopathology
D012739:Gonadal Steroid Hormones; D007473:Ion Channels; D013739:Testosterone; D011374:Progesterone
Arrhythmias; Cardiac repolarization; Gender difference; Sex hormones