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

Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, California

Submitted 24 March 2005 ; accepted in final form 20 April 2005

Intracellular calcium concentration ([Ca²⁺]_i) release from smooth endoplasmic reticulum (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 and subsequent pumping by SER Ca²⁺-ATPases. We measured [Ca²⁺]_i transients in isolated fura 2-loaded superior cervical ganglion cells from 6-, 12-, 20-, and 24-mo-old Fischer 344 rats. For rapid refilling, [Ca²⁺]_i transients were elicited by a 1) 5-s exposure to K⁺, 2) caffeine to release Ca²⁺ from SER stores, 3) K⁺ to refill SER Ca²⁺ stores, and 4) caffeine. The percent difference between the peak and rate of rise of the first and second caffeine-evoked [Ca²⁺]_i transient significantly declined over the age range of 12–24 mo. To estimate spontaneous refilling, cells were depolarized for 5 s with 68 mM K⁺ (control), followed by a 10-s exposure to 10 mM caffeine "conditioning stimulus" to deplete [Ca²⁺]_i stores. Caffeine was then rapidly applied for 5 s at defined intervals from 60 to 300 s. Integrated caffeine-evoked [Ca²⁺]_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 mo. Overall, these data suggest that the ability of superior cervical ganglion cells to sustain release of [Ca²⁺]_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.

store-operated calcium channels; calcium release; refilling of neuronal calcium stores; function of superior cervical ganglia

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