Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure

Keiko Igarashi-Saito, Hiroyuki Tsutsui, Shimako Yamamoto, Masaru Takahashi, Shintaro Kinugawa, Hirofumi Tagawa, Makoto Usui, Mitsutaka Yamamoto, Kensuke Egashira, Akira Takeshita

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Abstract

Sarcoplasmic reticulum (SR) Ca2+-ATPase gene expression is reduced in the failing myocardium. However, the functional relevance of these changes to myocardial contractility is not yet established. We assessed myocardial contractile function by analyzing sarcomere motion of isolated myocytes and also quantified SR Ca2+ regulatory protein gene expression by Northern blot analysis in the same hearts obtained from 10 dogs with pacing-induced heart failure (HF; 240 beats/min, 4 wk) and 7 control dogs. Sarcomere-shortening velocity was depressed in HF myocytes, accompanied by the prolongation of intracellular Ca2+ concentration ([Ca2+]i) transient measured by indo 1 fluorescence ratio. SR Ca2+-ATPase mRNA levels (normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly depressed in HF, and calsequestrin mRNA was increased. For control and HF dogs, sarcomere-shortening velocity correlated positively with Ca2+-ATPase mRNA levels (r = 0.73, n = 17, P < 0.01) but not with calsequestrin mRNA. Ca2+-ATPase mRNA levels were correlated with 45Ca2+ uptake rate by SR, which was also reduced in HF. Moreover, the inhibition of SR Ca2+-ATPase with thapsigargin or cyclopiazonic acid reproduced in normal myocytes the abnormalities observed in HF myocytes, such as depressed contractility and the prolonged [Ca2+]i transient duration. A downregulation of Ca2+-ATPase gene expression and a resultant decrease in Ca2+ uptake by SR may be responsible for the contractile dysfunction and the alterations of [Ca2+]i transient in HF.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume44
Issue number1
Publication statusPublished - Jul 1 1998

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Calcium-Transporting ATPases
Sarcoplasmic Reticulum
Tachycardia
Muscle Cells
Heart Failure
Messenger RNA
Sarcomeres
Calsequestrin
Dogs
Gene Expression
Glyceraldehyde-3-Phosphate Dehydrogenases
Thapsigargin
Regulator Genes
Northern Blotting
Myocardium
Down-Regulation
Fluorescence
Proteins

All Science Journal Classification (ASJC) codes

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

Cite this

Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure. / Igarashi-Saito, Keiko; Tsutsui, Hiroyuki; Yamamoto, Shimako; Takahashi, Masaru; Kinugawa, Shintaro; Tagawa, Hirofumi; Usui, Makoto; Yamamoto, Mitsutaka; Egashira, Kensuke; Takeshita, Akira.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 44, No. 1, 01.07.1998.

Research output: Contribution to journalArticle

Igarashi-Saito, K, Tsutsui, H, Yamamoto, S, Takahashi, M, Kinugawa, S, Tagawa, H, Usui, M, Yamamoto, M, Egashira, K & Takeshita, A 1998, 'Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure', American Journal of Physiology - Heart and Circulatory Physiology, vol. 44, no. 1.
Igarashi-Saito, Keiko ; Tsutsui, Hiroyuki ; Yamamoto, Shimako ; Takahashi, Masaru ; Kinugawa, Shintaro ; Tagawa, Hirofumi ; Usui, Makoto ; Yamamoto, Mitsutaka ; Egashira, Kensuke ; Takeshita, Akira. / Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure. In: American Journal of Physiology - Heart and Circulatory Physiology. 1998 ; Vol. 44, No. 1.
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