Abstract:
It is generally agreed that changes in Ca2+ 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 [Ca2+]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 Ca2+ transients were bigger (peak [Ca2+]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 Ca2+ 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 Ca2+, 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 Ca2+ extrusion. This view was supported by a slower decay of caffeine-induced Ca2+ 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.