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10.1253/circj.CJ-20-0310

http://scihub22266oqcxt.onion/10.1253/circj.CJ-20-0310
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suck abstract from ncbi


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pmid32554946      Circ+J 2020 ; 84 (8): 1244-1253
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  • Magnesium Deficiency Causes Transcriptional Downregulation of Kir2 1 and Kv4 2 Channels in Cardiomyocytes Resulting in QT Interval Prolongation #MMPMID32554946
  • Shimaoka T; Wang Y; Morishima M; Miyamoto S; Ono K
  • Circ J 2020[Jul]; 84 (8): 1244-1253 PMID32554946show ga
  • BACKGROUND: Mechanisms for QT interval prolongation and cardiac arrhythmogenesis in hypomagnesemia are poorly understood. This study investigated the potential molecular mechanism for QT prolongation caused by magnesium (Mg) deficiency in rats by using the patch clamp technique and molecular biology.Methods and Results:Male Wistar rats were fed an Mg-free diet or a normal diet for up to 12 weeks. There was QT prolongation in the ECG of Mg-deficient rats, and cardiomyocytes from these rats showed prolongation of action potential duration. Electrophysiological studies showed that inward-rectifying K(+)current (I(K1)) and transient outward K(+)current (I(to)) were decreased in Mg-deficient cardiomyocytes, and these findings were consistent with the downregulation of mRNA, as well as protein levels of Kir2.1 and Kv4.2. In Mg-deficient cardiomyocytes, transcription factors, GATA4 and NFAT, were upregulated, whereas CREB was downregulated. In contrast to Mg deficiency, cellular Mg(2+)overload in cultured cardiomyocytes resulted in the upregulation of Kir2.1 and Kv4.2, which was accompanied by the downregulation of GATA4 and NFATc4, and the upregulation of CREB. Activation of NFAT and inhibition of CREB reduced Kv4.2-I(to), whereas Kir2.1-I(K1)was reduced by CREB inhibition but not by NFTA activation. CONCLUSIONS: Intracellular Mg deficiency downregulates I(K1)and I(to)in cardiomyocytes, and this is mediated by the transcription factors, NFAT and CREB. These results provide a novel mechanism for the long-term QT interval prolongation in hypomagnesemia.
  • |*Action Potentials[MESH]
  • |*Heart Rate[MESH]
  • |Animals[MESH]
  • |Arrhythmias, Cardiac/*etiology/genetics/metabolism/physiopathology[MESH]
  • |Disease Models, Animal[MESH]
  • |Down-Regulation[MESH]
  • |Magnesium Deficiency/*complications[MESH]
  • |Male[MESH]
  • |Myocytes, Cardiac/*metabolism[MESH]
  • |Potassium Channels, Inwardly Rectifying/genetics/*metabolism[MESH]
  • |Rats, Wistar[MESH]
  • |Shal Potassium Channels/genetics/*metabolism[MESH]
  • |Signal Transduction[MESH]
  • |Time Factors[MESH]


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