Calcium spark properties in ventricular myocytes are altered in aged mice

This study determined whether whole cell Ca2+ transients and unitary sarcoplasmic reticulum (SR) Ca2+ release events are constant throughout adult life or whether Ca2+ release is altered in aging ventricular myocytes. Myocytes were isolated from young adult (∼5 mo old) and aged (∼24 mo old) mice. Spontaneous Ca2+ sparks and Ca 2+ transients initiated by field stimulation were detected with fluo-4. All experiments were conducted at 37°C. Ca2+ transient amplitudes were reduced, and Ca2+ transient rise times were abbreviated in aged cells stimulated at 8 Hz compared with young adult myocytes. Furthermore, the incidence and frequency of spontaneous Ca2+ sparks were markedly higher in aged myocytes compared with young adult cells. Spark amplitudes and spatial widths were similar in young adult and aged myocytes. However, spark half-rise times and half-decay times were abbreviated in aged cells compared with younger cells. Resting cytosolic Ca2+ levels and SR Ca2+ stores were assessed by rapid application of caffeine in fura-2-loaded cells. Neither resting Ca2+ levels nor SR Ca 2+ content differed between young adult and aged cells. Thus increased spark frequency in aging cells was not attributable to increased SR Ca2+ stores. Furthermore, the decrease in Ca2+ transient amplitude was not due to a decrease in SR Ca2+ load. These results demonstrate that alterations in fundamental SR Ca2+ release units occur in aging ventricular myocytes and raise the possibility that alterations in Ca2+ release may reflect age-related changes in fundamental release events rather than changes in SR Ca2+ stores and diastolic Ca2+ levels. Copyright © 2006 the American Physiological Society.