Non-steady-state calcium handling in failing hearts from the spontaneously hypertensive rat

Marie-Louise Ward, David J Crossman, Denis S Loiselle, Mark B Cannell

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9 Citations (Scopus)

Abstract

It is generally agreed that changes in Ca(2+) cycling are often associated with heart failure, yet the impact of these changes on a beat-to-beat basis remains unclear. Measurements of isometric force and [Ca(2+)](i) were made at 37°C in left ventricular trabeculae from failing spontaneously hypertensive rat (SHR) hearts, and their normotensive Wistar-Kyoto (WKY) controls. At 1 Hz, peak stress was reduced in SHR (14.5 ± 2.4 mN mm(-2) versus 22.5 ± 6.7 mN mm⁻² for WKY), although the Ca(2+) transients were bigger (peak [Ca(2+)](i) 0.60 ± 0.08 μM versus 0.38 ± 0.03 μM for WKY) with a slower decay of fluorescence (time constant 0.105 ± 0.005 s versus 0.093 ± 0.002 s for WKY). To probe dynamic Ca(2+) cycling, two experimental protocols were used to potentiate force: (1) an interval of 30 s rest, and (2) a 30-s train of paired-pulses, and the recirculation fraction (RF) calculated for recovery to steady-state. No difference was found between rat strains for RF calculated from either peak force or Ca(2+), although the RF was dependent on potentiation protocol. Since SR uptake is slower in SHR, the lack of change in RF must be due to a parallel decrease in trans-sarcolemmal Ca(2+) extrusion. This view was supported by a slower decay of caffeine-induced Ca(2+) transients in SHR trabeculae. Confocal analysis of LV free wall showed t-tubules were distorted in SHR myocytes, with reduced intensity of NCX and SERCA2a labelling in comparison to WKY.
Original languageEnglish
Pages (from-to)991-1001
Number of pages11
JournalPflügers Archiv European Journal of Physiology
Volume460
Issue number6
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Animals
  • Calcium
  • Heart Failure
  • Heart Ventricles
  • Myocardial Contraction
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sarcolemma
  • Sarcoplasmic Reticulum
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Sodium-Calcium Exchanger

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