title: Synergistic restoring effects of isoproterenol and magnesium on KCNQ1-inhibited bradycardia cell models cultured in microelectrode array.
abstract: OBJECTIVE
  Bradycardia is caused by loss-of-function mutations in potassium channels that regulate phase 3 repolarization of the cardiac action potential. The purpose of this study is to monitor the effects of potassium channel (KCNQ1) inhibition and to evaluate the effects of isoproterenol (ISO) and MgSO4 in restoring sinus rhythm in atrial cells.
  
  
  METHODS
  Microelectrode array was used to analyze conduction velocity, voltage amplitude and cycle length of atrial cells (HL-1). A combination of ISO and MgSO4 was used to restore sinus rhythm in these cells.
  
  
  RESULTS
  mRNA expression levels of KCNQ1 (42.2 vs. 100%, p < 0.0001), connexin 43 (29.6 vs. 100%, p = 0.0033), atrial natriuretic peptide (31.0 vs. 100%, p = 0.0030), cardiac actin (38.2 vs. 100%, p < 0.0001) and α-myosin heavy chain (31.2 vs. 100%, p = 0.00254) were significantly lower in the KCNQ1 gene-inhibited group compared to the control group. When treated with MgSO4 (1 mM) and ISO (10 μM), conduction velocity (0.0208 ± 0.0036 vs. 0.0086 ± 0.0014 m/s, p = 0.0004) and voltage amplitude (1,210.78 ± 65.81 vs. 124.1 ± 13.30 μV, p < 0.0001) were higher, and cycle length (431.55 ± 2.05 vs. 1,015.15 ± 4.31 ms, p < 0.0001) was shorter than in the gene-inhibited group.
  
  
  CONCLUSIONS
  Inhibition of sinus rhythm in the bradycardia cell model was recovered by treatment with ISO and MgSO4, demonstrating the potency of combination therapy in the treatment of bradycardia.
authors: Department of Biomedical Engineering, Medical College, Korea University, Seoul, Republic of Korea.
authors: Sook Kyoung
authors: SK
authors: Kim
authors: Hui-Nam
authors: HN
authors: Pak
authors: Yongdoo
authors: Y
authors: Park
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000188:drug therapy* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use*; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008278:Magnesium Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D002316:Cardiotonic Agents; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D034741:RNA, Small Interfering; D008278:Magnesium Sulfate; D007545:Isoproterenol