title: Hypomagnesemic down-regulation of L-type Ca(2+) channel in cardiomyocyte as an arrhythmogenic substrate in rats.
abstract: The present study was designed to investigate the effect of magnesium (Mg) depletion on the expression of voltage-gated calcium (Ca(2+)) channels and Ca(2+) currents in the heart and thereby on hypomagnesemic arrhythmogenesis in adult male rats. Male Wistar rats were fed an Mg-free diet or a normal diet for up to 16 weeks. Serum Mg concentrations were significantly reduced at week 4 or later with an Mg-free diet, which experimentally represents hypomagnesemia. Myocardial Mg contents were also reduced at week 16 accompanied by myocardial hypertrophy. Telemetric ECG recordings revealed a long-term changes of ECG parameters in hypomagnesemic rats; RR shortening, QT prolongation and appreciable PR prolongation. At the same time, hypomagnesemic rats demonstrate various bradycardiac arrhythmias including ventricular premature beats, atrioventricular blocks and sinus arrest, which were never recoded in rats fed by a normal diet. Electrophysiological studies elucidated that the L-type Ca(2+) channel current was decreased in Mg-deficient cardiomyocytes, and these findings were consistent with down-regulation of CaV1.2-mRNA but not in levels of CaV1.3, CaV3.1 or CaV3.2. These findings provide novel insights into hypomagnesemic electrophysiological disorders in the heart, and should be considered when assessing the design of effective antiarrhythmic treatments in patients with hypomagnesemia.
authors.affiliation: Department of Pathophysiology, Oita University School of Medicine, Yufu, Oita 879-5593, Japan; Department of Cardiovascular Surgery, Oita University School of Medicine, Yufu, Oita 879-5593, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shimaoka
authors.affiliation: Department of Pathophysiology, Oita University School of Medicine, Yufu, Oita 879-5593, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Oita University School of Medicine, Yufu, Oita 879-5593, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Morishima
authors.affiliation: Department of Cardiovascular Surgery, Oita University School of Medicine, Yufu, Oita 879-5593, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Pathophysiology, Oita University School of Medicine, Yufu, Oita 879-5593, Japan. Electronic address: ono@oita-u.ac.jp.
authors.forename: Katsushige
authors.initials: K
authors.lastname: Ono
keywords: Ca(2+) channel; Ca(2+) current; Ca(V)1.2; Hypomagnesemia; Magnesium