Down-regulation of the small conductance calcium-activated potassium channels in diabetic mouse atria

Fu Yi, Tian You Ling, Tong Lu, Xiao Li Wang, Jingchao Li, William C. Claycomb, Win Kuang Shen, Hon Chi Lee

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The small conductance Ca2+-activated K+ (SK) channels have recently been found to be expressed in the heart, and genome-wide association studies have shown that they are implicated in atrial fibrillation. Diabetes mellitus is an independent risk factor of atrial fibrillation, but the ionic mechanism underlying this relationship remains unclear. We hypothesized that SK channel function is abnormal in diabetes mellitus, leading to altered cardiac electrophysiology. We found that in streptozotocin-induced diabetic mice, the expression of SK2 and SK3 isoforms was down-regulated by 85 and 92%, respectively, whereas that of SK1 was not changed. SK currents from isolated diabetic mouse atrial myocytes were significantly reduced compared with controls. The resting potentials of isolated atrial preparations were similar between control and diabetic mice, but action potential durations were significantly prolonged in the diabetic atria. Exposure to apamin significantly prolonged action potential durations in control but not in diabetic atria. Production of reactive oxygen species was significantly increased in diabetic atria and in high glucose-cultured HL-1 cells, whereas exposure of HL-1 cells in normal glucose culture to H2O2 reduced the expression of SK2 and SK3. Tyrosine nitration in SK2 and SK3 was significantly increased by high glucose culture, leading to accelerated channel turnover. Treatment with Tiron prevented these changes. Our results suggest that increased oxidative stress in diabetes results in SK channel-associated electrical remodeling in diabetic atria and may promote arrhythmogenesis.

Original languageEnglish (US)
Pages (from-to)7016-7026
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number11
DOIs
StatePublished - Mar 13 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Down-regulation of the small conductance calcium-activated potassium channels in diabetic mouse atria'. Together they form a unique fingerprint.

  • Cite this