IMPACT OF ADVANCING AGE ON CAFFEINE MEDIATED SENSITIZATION OF CALCIUM RELEASE IN SUPERIOR CERVICAL GANGLION CELLS.

In vascular sympathetic neurons calcium‐induced calcium release (CICR) is mediated by ryanodine receptors (RyR) and contributes to the magnitude of stimulation‐evoked intracellular calcium ([Ca 2+ ]i) transients. Furthermore, this process can be sensitized with RyR agonists such as caffeine. In this study we assessed the contribution of CICR to the magnitude of electric field stimulation (EFS)‐evoked [Ca 2+ ]i transients. We measured EFS‐evoked changes in [Ca 2+ ]i in isolated fura‐2 loaded superior cervical ganglion (SCG) cells, from F‐344 rats aged 6, 12, and 24 months. EFS was delivered over a range of 3 to 24 pulses (3Hz) in the absence and presence of 5mM caffeine. Maximal EFS‐evoked increases in [Ca 2+ ]i significantly increased from 6‐12 months and then declined at 24 months, suggesting that CICR as a component of the EFS‐evoked [Ca 2+ ]i transient declines with age. However, most interestingly, caffeine significantly increased EFS‐evoked [Ca 2+ ]i transients over the entire stimulation range (3–24 pulses) in all age groups. In addition, caffeine decreased the number of pulses to achieve ½ maximal EFS‐evoked [Ca 2+ ]i in all age groups. Taken together, the data suggest that with advancing age although the contribution of CICR to EFS‐evoked [Ca 2+ ]i transients may decline with age, some of this function can be reclaimed in the presence of RyR agonists such as caffeine. Supported in part by NIH HED P01 #31226