Altered cardiac excitation-contraction coupling in ventricular myocytes from spontaneously diabetic BB rats

Jun Ren, Ann M. Bode

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Cardiac excitation-contraction (E-C) coupling abnormalities in chemically induced diabetes have been well defined. Heart dysfunction has also been reported in diabetes of genetic origin. The purpose of this study was to determine whether heart dysfunction in genetically predisposed diabetes is attributable to impaired E-C coupling at the cellular level. Myocytes were isolated from 1-yr-old BioBreed (BB) spontaneously diabetic-prone (BB/DP) rats and their diabetic-resistant littermates (BB/DR). Mechanical properties were evaluated by use of a video edge-detection system. Myocytes were electrically stimulated at 0.5 Hz. The contractile properties analyzed included peak shortening (PS), time-to-peak shortening (TPS), time-to-90% relengthening (TP90), and maximal velocities of shortening and relengthening (±dL/dt). Intracellular Ca2+ handling was evaluated with fura 2 fluorescent dye. Myocytes from spontaneously diabetic hearts exhibited a depressed PS, prolonged TPS and TRbs90, and reduced ±dL/dt. Consistent with the mechanical response, myocytes from the BB/DP group displayed reduced resting and peak intracellullar Ca2+ concentration associated with a slowed Ca2+-transient decay. Furthermore, myocytes from BB/DP hearts were less responsive to increases in extracellular Ca2+ and norepinephrine and equally responsive to increases in stimulation frequency and KCl compared with those from the BB/DR group. These results suggest that the genetic diabetic state produces altered cardiac E-C coupling, in part, because of abnormalities of the myocyte, similar to that demonstrable after chemically induced diabetes or during human diabetes.

Original languageEnglish (US)
Pages (from-to)H238-H244
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number1 48-1
DOIs
StatePublished - 2000

Keywords

  • BioBreed rat
  • Genetic diabetes mellitus
  • Intracellular calcium ion transients
  • Relaxation

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