U73122 inhibits volgtage-gated Ca2+ currents in rat endocrine cells

• 作 者: Dan-Dan Feng Zi-Qiang Luo Chen Chen
• 机 构: Department of Physiology,Xiangya Medical School,Central South University,Changsha,China
• 出 处: International Conference for Physiological Sciences 2012(201
• 发表日期: 2012年8期
• 关键词: U73122 voltage-gated Ca2+currents endocrine cells

　　U73122 is often used as a selective amino-steroid phospholipase C (PLC) inhibitor, which has been widely applied to exclude intracellular Ca2+ release from InsP3 sensitive storage sites from the triggered increase in [Ca2+]i.lnsP3 is the downstream product of PLC and blockade of PLC will reduce InsP3 production and induced Ca2+ release.Ca2+ influx through membrane Ca2+ channels will also cause an increase in [Ca2+]i.In order to evaluate the specificity of U73122, patch clamp recordings were performed on primary cultured rat pancreatic β-cells and two representative endocrine cell lines, insulin secreting INS-1 cells and growth hormone secreting GH3 cells.Application of U73122 or its inactive analogue U73343 directly and irreversibly inhibited the voltage-gated Ca2+ currents in rat pancreatic β-cells, INS-1 and GH3 cells.This inhibition was dose dependent and occurred immediately after application onto the recorded cells, which suggested a direct action on membrane ion channels.This unexpected result suggests that U73122 may directly inhibit Ca2+-influx through membrane voltage-gated Ca2+ channels, besides the inhibition of InsP3 production and intracellular Ca2+ release in these two endocrine cells.U73122 should, therefore, be used with caution to conclude source of Ca2+ for the increase in [Ca2+]i, at least in these two cell types.