Role of Ca2+ availability to myofilaments and their sensitivity to Ca2+ in myocyte contractile dysfunction in heart failure

Shintaro Kinugawa, Hiroyuki Tsutsui, Shinji Satoh, Masaru Takahashi, Tomomi Ide, Keiko Igarashi-Saito, Ken ichi Arimura, Kensuke Egashira, Akira Takeshita

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10 Citations (Scopus)

Abstract

Objective: Contractile function is depressed at the isolated myocyte level in heart failure (HF), which could result from the decreased availability of intracellular calcium ([Ca2+]i) to the myofibrils and/or the depressed sensitivity of myofilaments to [Ca2+]i. However, the cellular basis of contractile dysfunction remains unestablished. Methods: We isolated left ventricular myocytes from dogs with rapid pacing-induced HF. Cell shortening and [Ca2+]i transients were measured by indo-1 fluorescence and the myofilament Ca2+ sensitivity was analyzed by the shortening-[Ca2+]i relation in intact myocytes as well as by the pCa-tension relation in skinned cells. Results: Peak cell shortening magnitude was depressed in HF, associated with a parallel decrease of [Ca2+]i transient amplitude. There was a significant positive correlation between these two variables (r=0.71, P<0.01). In contrast, myofibrillar sensitivity to Ca2+, determined by both intact and skinned myocytes, was comparable between control and HF. Further, there was no significant difference in Ca2+ sensitivity between control and HF even at shorter (1.8 μm) or longer (2.2 μm) sarcomere length. Conclusions: Using both intact and skinned cellular preparations, a potential defect in myocyte contractile function in HF was a reduction in Ca2+ availability to the myofilaments, rather than the inherent defects in myofilament sensitivity to Ca2+. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)398-406
Number of pages9
JournalCardiovascular research
Volume44
Issue number2
DOIs
Publication statusPublished - Nov 1 1999

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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