Synergistic restoring effects of isoproterenol and magnesium on KCNQ1-inhibited bradycardia cell models cultured in microelectrode array

Sook Kyoung Kim, Hui Nam Pak, Yongdoo Park

Research output: Contribution to journalArticle

Abstract

Objectives: 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 MgSO 4 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 MgSO 4 (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. Conclusion: 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.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalCardiology (Switzerland)
Volume128
Issue number1
DOIs
Publication statusPublished - 2014 Apr

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Synergistic restoring effects of isoproterenol and magnesium on KCNQ1-inhibited bradycardia cell models cultured in microelectrode array'. Together they form a unique fingerprint.

  • Cite this