Ca2+ 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. Ca2+ transients were evoked by 40ms voltage-clamp pulses depolarising at 0.4, 1, 2, 4 or 8Hz. At 8Hz, Ca2+ transients from senescent cells peaked later (39ms versus 23ms) to smaller systolic [Ca2+](c) (667nM versus 1110nM) and decayed at slower rate (16s(-1) versus 33s(-1)) to higher end-diastolic [Ca2+](c) (411nM versus 220nM) 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 Ca2+ inward current. Since concentrations of SERCA2a and SERCA2b proteins were similar in young and senescent cells, slow rate of Ca2+ decay and high diastolic [Ca2+]c are explained on the assumption that the usual Ca2+ stimulation of SERCA2 activity is attenuated in senescent cells. The prolonged time-to-peak [Ca2+]c is discussed to result from insufficient SR Ca2+ 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 Ca2+ transients are discussed to cause systolic and diastolic failure if senescent mouse hearts beat at high frequencies.
Isenberg
G
G
Department of Physiology, Martin-Luther-University Halle, Halle 06097, Germany. Gerrit.Isenberg@medizin.uni-halle.de
Borschke
B
B
Rueckschloss
U
U
D000185:Actinin / Q000032:analysis; D000375:Aging / Q000502:physiology*; D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D020746:Calcium Channels, L-Type; D007211:Indoles; D000185:Actinin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D000252:Calcium-Transporting ATPases; C048960:indo-1; D002118:Calcium