A Novel Effect of Cyclic AMP on Capacitative Ca super(2+) Entry in Cultured Rat Cerebellar Astrocytes

• Published in: Journal of neurochemistry 1999-09, Vol.73 (3), p.1318-1328
• Main Authors: Wu, Mei-Lin, Chen, Wei-Hao, Liu, I-Hsiu, Tseng, Chuen-Den, Wang, Seu-Mei
• Format: Article
• Language: English
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.1999.0731318.x

One of the most important intracellular Ca super(2+) regulatory mechanisms in nonexcitable cells, "capacitative Ca super(2+) entry" (CCE), has not been adequately studied in astrocytes. We therefore investigated whether CCE exists in cultured rat cerebellar astrocytes and studied the roles of cyclic AMP (cAMP) and protein kinase C (PKC) in CCE. We found that (1) at least two different intracellular Ca super(2+) stores, the endoplasmic reticulum and mitochondria, are present in cerebellar astrocytes; (2) CCE does exist in these cells and can be inhibited by Ni super(2+), miconazole, and SKF 96365; (3) CCE can be directly enhanced by an increase in intracellular cAMP, as 8-bromoadenosine 3',5'-cyclic monophosphate (8-brcAMP), forskolin, and isobutylmethylxanthine have stimulatory effects on CCE; and (4) neither of the two potent protein kinase A (PKA) inhibitors, H8 and H89, nor a specific PKA agonist, Sp-adenosine 3',5'-cyclic monophosphothioate, had a significant effect on cAMP-enhanced Ca super(2+) entry. The [Ca super(2+)] sub(i) increase was not due to a release from calcium stores, hyperpolarization of the membrane potential, inhibition of calcium extrusion, or a change in pH sub(i), suggesting that cAMP itself probably acts as a novel messenger to modulate CCE. We also conclude that activation of PKC results in an increase in CCE. cAMP and PKC seem to modulate CCE by different pathways.