title: Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice.
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 degrees 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 micromol/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Clinical Research, Osaka National Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: N G
authors.initials: NG
authors.lastname: Perez
authors.forename: H
authors.initials: H
authors.lastname: Kusuoka
authors.forename: D L
authors.initials: DL
authors.lastname: Baker
authors.forename: M
authors.initials: M
authors.lastname: Periasamy
authors.forename: E
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*
chemical_list: D000252:Calcium-Transporting ATPases; D002118:Calcium