Advancing age alters the contribution of release of calcium from internal stores to stimulation‐evoked calcium transients

Abstract

In vascular adrenergic neurons the release of calcium from SER stores known as calcium induced calcium release (CICR) plays a role in determining the magnitude and shape of stimulation-evoked intracellular calcium ([Ca2+]i) transients. The release of calcium is triggered by activation of ryanodine receptor (RYR) channels. We measured electric field stimulation (EFS)-evoked [Ca2+]i transients in isolated fura-2 loaded superior cervical ganglion (SCG) cells from F-344 rats aged 6, 12 and 24 months. 50 square-wave pulses of EFS (5Hz) were delivered using a Grass stimulator via platinum electrodes. The current was ramped from 50–300 mA in the absence (control) and presence of the RYR antagonist, ryanodine (100 μM) to block release of calcium from SER stores. EFS-evoked changes in peak and rate of rise of [Ca2+]i significantly declined by 43% and 59% respectively in SCG cells from 24 month-old animals as compared to 6 and 12 months (P<0.05 by ANOVA). Following the addition of ryanodine, EFS-evoked changes in peak and rate of rise of [Ca2+]i significantly declined by 22% and 25% respectively only in SCG cells from 6 and 12 month-old animals with no effect at 24 months (P<0.03 by paired T-test). In addition, following blockade of CICR the dynamics of EFS-evoked [Ca2+]i transients in young cells is similar to old. These data suggest that in SCG cells there is an age-related decline in the contribution of CICR in determining the magnitude and shape of EFS-evoked [Ca2+]i transients. Supported in part by NIH HED P01 #31226