Ca super(2+) transients of cardiomyocytes from senescent mice peak late and decay slowly

Ventricular myocytes were isolated from either young (2 months, 'young myocytes') or senescent (20-26 months, 'senescent myocytes') mice. Ca super(2+) transients were evoked by 40 ms voltage-clamp pulses depolarising at 0.4, 1, 2, 4 or 8 Hz. At 8 Hz, Ca super(2+) transients from senescent cells peaked later (39 ms versus 23 ms) to smaller systolic [Ca super(2+)] sub(c) (667 nM versus 1110 nM) and decayed at slower rate (16 s super(-1) versus 33 s super(-1)) to higher end-diastolic [Ca super(2+)] sub(c) (411 nM versus 220 nM) than those from young myocytes. These differences were less pronounced at lower frequencies of pulsing and could not be explained by differences of the time integral of Ca super(2+) inward current. Since concentrations of SERCA2a and SERCA2b proteins were similar in young and senescent cells, slow rate of Ca super(2+) decay and high diastolic [Ca super(2+)] sub(c) are explained on the assumption that the usual Ca super(2+) stimulation of SERCA2 activity is attenuated in senescent cells. The prolonged time-to-peak [Ca super(2+)] sub(c) is discussed to result from insufficient SR Ca super(2+) filling by SERCA2 and, in context with confocal images, from a shift of the SERCA2b distribution to the subsarcolemmal space. The age-related changes of the Ca super(2+) transients are discussed to cause systolic and diastolic failure if senescent mouse hearts beat at high frequencies.