2‐APB mediated effects on hypoxic calcium influx in rat carotid body glomus cells

Abstract

Hypoxia depolarizes the glomus cells of the carotid body and induces calcium rise which was reversed by 2‐APB, an inhibitor of store‐operated calcium channels situated in the endoplasmic reticulum (ER), whereas those by hypercapnia and high extracellular [K+] were not, although both hypoxia and hypercapnia depolarize the glomus cells. Hypoxia‐dependent calcium rise was triggered by a reduction of IP3‐receptors and 2‐APB significantly reversed this response. Further, mitochondrial inhibitions completely overlapped the 2‐APB inhibition, suggesting same mechanism of effects. Also, ATP elevated the [Ca2+]i in normoxia due to calcium influx and the release from the [Ca2+]i stores, both of which were inhibited by 2‐APB. This reaction, as revealed by 2‐APB, is unique and is due to possible involvement of phosphorylation mechanisms in hypoxia, and not operated in hypercapnia. Therefore we hypothesize that store‐operated calcium channels in the ER, where IP3 receptors reside, is reacted with 2‐APB and is critical for the inhibitory response. However, 2‐APB did not block hypercapnic‐ and high extracellular [K+]‐dependent calcium increase.Hypercapnia and high extracellular K+ have no access to this [Ca2+]i stores of ER, and hence have no effects.Supported by NIH grant 43413.