Transient elevation of glucose increases arrhythmia susceptibility in non-diabetic rat trabeculae with non-uniform contraction

Masahito Miura, Tetsuya Handoh, Yuhto Taguchi, Taiki Hasegawa, Yui Takahashi, Natsuki Morita, Ayana Matsumoto, Chiyohiko Shindoh, Haruka Sato

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: In non-diabetic patients with acute coronary syndrome, stress hyperglycemia occasionally occurs and is related to their mortality. Whether transient elevation of glucose affects arrhythmia susceptibility in non-diabetic hearts with non-uniform contraction was examined. Methods and Results: Force, intracellular Ca2+ ([Ca2+]i), and membrane potential were measured in trabeculae from rat hearts. Non-uniform contraction was produced by a jet of paralyzing solution. Ca2+ waves and arrhythmias were induced by electrical stimulation (2.0 mmol/L [Ca2+]o). The activity of Ca2+/calmodulin-dependent protein kinaseII (CaMKII) was measured. An elevation of glucose from 150 to 400 mg/dL increased the velocity of Ca2+ waves and the number of spontaneous action potentials triggered by electrical stimulation. Besides, the elevation of glucose increased the CaMKII activity. In the presence of 1 μmol/L KN-93, the elevation of glucose did not increase the velocity of Ca2+ waves and the number of triggered action potentials. In addition, in the presence of 1 μmol/L autocamtide-2 related inhibitory peptide or 50 μmol/L diazo-5-oxonorleucine, the elevation of glucose did not increase the number of triggered action potentials. Furthermore, the elevation of glucose by adding L-glucose did not increase their number. Conclusions: In non-diabetic hearts with non-uniform contraction, transient elevation of glucose increases the velocity of Ca2+ waves by activating CaMKII,probably through glycosylation with O-linked β-N-acetylglucosamine, thereby increasing arrhythmia susceptibility.

Original languageEnglish
Pages (from-to)551-558
Number of pages8
JournalCirculation Journal
Volume84
Issue number4
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Arrhythmia
  • Calcium wave
  • Glucose

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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