Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice

Katsuji Hashimoto, Nestor Gustavo Perez, Hideo Kusuoka, Debra L. Baker, Muthu Periasamy, Eduardo Marbán

Research output: Contribution to journalArticle

Abstract

Objective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is frequency-dependent, as might be expected if attributable to changes in SR Ca2+ loading. Methods: Intracellular [Ca2+] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n = 6) or SERCA2a transgenic (n = 6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca2+ transients (transgenics: 1.56 ± 0.09 μmol/L, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm2, controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P<0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.

Original languageEnglish (US)
Pages (from-to)144-151
Number of pages8
JournalBasic Research in Cardiology
Volume95
Issue number2
DOIs
StatePublished - Apr 2000

Keywords

  • Ca-pump
  • Calcium
  • Contractile function
  • E-c coupling
  • SR

ASJC Scopus subject areas

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

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    Hashimoto, K., Perez, N. G., Kusuoka, H., Baker, D. L., Periasamy, M., & Marbán, E. (2000). Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice. Basic Research in Cardiology, 95(2), 144-151. https://doi.org/10.1007/s003950050176