Capacitative Ca super(2+) influx in glial cells is inhibited by glycolytic inhibitors

• Published in: Glia 1997-11, Vol.21 (3), p.315-326
• Main Authors: Wu, Mei-Lin, Kao, E-Fong, Liu, I-Hsiu, Wang, Bor-Sen, Lin-Shiau, Shoei-Yn
• Format: Article
• Language: English
• ISSN: 0894-1491

In non-excitable cells, stimulation of phosphoinositide (PI) turnover and inhibition of the endoplasmic reticulum (ER) Ca super(2+)-ATPase are methods commonly used to deplete calcium stores, resulting in a capacitative Ca super(2+) influx (i.e., Ca super(2+) release-activated Ca super(2+) influx). Since this Ca super(2+) influx in glial cells has not been thoroughly investigated, we have used C sub(6) glioma cells as a glial cell model to study this phenomenon. On adding cyclopiazonic acid (CPA) or thapsigargin (TG) (two ER Ca super(2+)-ATPase inhibitors) in Ca super(2+)-free medium, only a small transient increase in intracellular Ca super(2+) was seen. After depletion of the stored Ca super(2+), a marked Ca super(2+) influx, followed by a prolonged plateau, was seen on re-addition of extracellular Ca super(2+) ions (2 mM), i.e., capacitative Ca super(2+) influx. A similar effect was seen on adding ATP, known to deplete the inositol triphosphate (IP sub(3))-sensitive Ca super(2+) store in C sub(6) cells. After various degrees of store depletion, the amplitude of the capacitative Ca super(2+) influx was found to be highly dependent on the amount of Ca super(2+) remaining in the store. This Ca super(2+) influx was markedly inhibited by (1) La super(3+) and Ni super(2+), (2) SK&F 96365, econazole, and miconazole, and (3) membrane depolarization, clearly showing that this Ca super(2+) influx after store depletion in C sub(6) cells is a capacitative mechanism. Interestingly, the capacitative Ca super(2+) influx can be inhibited by a reduction in intracellular ATP (ATP sub(i)) levels in glial cells. The role of ATP sub(i) in the capacitative Ca super(2+) influx is discussed.