Research reportModulation of ultra-low-molecular-weight heparin on [Ca2+]i in nervous cells

Heparin is an effective competitive antagonist of inositol 1,4,5-trisphosphate receptors (IP3Rs). It binds to IP3Rs and affects calcium homeostasis. Ultra-low-molecular-weight heparin (ULMWH) is heparin's derivative, the present study was designed to test the effects of ULMWH on intracellular calcium concentration ([Ca2+]i) in primary cultured neurons. [Ca2+]i was measured by Multilabel Counter Victor-1420 using Fura-2/AM as the calcium fluorescent probe. The results indicated that ULMWH decreased the resting [Ca2+]i with or without extracellular Ca2+. They had no effects on high K+-induced elevation of intracellular Ca2+ level indicating that ULMWH had no effect on external Ca2+ influx mediated by voltage-dependent calcium channels. However, they partially reduced the increase in [Ca2+]i induced by glutamate. Furthermore, ULMWH significantly inhibited the inositol 1,4,5-trisphosphate (IP3)-induced increase in [Ca2+]i both in cellular and subcellular level. These results suggest that ULMWH may reduce [Ca2+]i in neurons through suppressing Ca2+ release from IP3-sensitive stores.

► ULMWH seems to cross the BBB and causes lower risk of bleeding. ► It is the first study about the beneficial effects of ULMWH on [Ca2+]i. ► The mechanism involves in suppressing IP3-mediated Ca2+release. ► We isolated ER and mitochondria using subcellular fractionation. ► ULMWH might act as a useful agent in the prevention and treatment in AD.