Advancing age alters rapid and spontaneous refilling of caffeine sensitive calcium stores in sympathetic superior cervical gang

Intracellular calcium ([Ca]i) release from SER stores plays an important role in cell signaling. These stores are rapidly refilled via influx through voltage gated calcium channels or spontaneously via store-operated calcium channels (SOCC), and subsequent pumping by smooth endoplasmic reticulum Ca -ATPases (SERCA). We measured [Ca]i transients in isolated Fura-2 loaded superior cervical ganglion (SCG) cells from 6, 12, 20 and 24 month-old F-344 rats. For rapid refilling, [Ca]i transients were elicited by a 5 sec exposure to K (S1), caffeine to release Ca from SER stores (S2), K to refill SER Ca stores (S3), and caffeine (S4). The % difference between the peak and rate of rise of the first and second caffeineevoked [Ca]i transient significantly declined over the age range of 12-24 months. To estimate spontaneous refilling, cells were depolarized for 5 sec with 68 mM K (control), followed by a 10 sec exposure to 10 mM caffeine "conditioning stimulus" to deplete [Ca]i stores. Caffeine was then rapidly applied for 5 sec at defined intervals from 60 to 300 sec. Integrated caffeine-evoked [Ca]i transients were measured and plotted as a percentage of the K response vs. time. The derivative of the refilling time curves significantly declined over the age range from 12-24 months. Overall, these data suggest that the ability of SCG cells to sustain release of [Ca]i, following rapid or spontaneous refilling declines with advancing age. Compromised ability to sustain calcium signaling may possibly alter the overall function of adrenergic neurons innervating the cerebrovasculature.