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Calcium spark properties in ventricular myocytes are altered in aged mice

Susan E. Howlett, Scott A. Grandy, and Gregory R. Ferrier

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada

Submitted 23 June 2005 ; accepted in final form 23 November 2005

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 Ca²⁺ 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 Ca²⁺ 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.

senescence; sarcoplasmic reticulum; Ca²⁺ imaging; fluorescence; excitation-contraction coupling