The 2-aminoethoxydiphenyl borate analog, DPB161 blocks store-operated Ca2+ entry in acutely dissociated rat submandibular cells
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Kunkun Xia1,2,*, Zegang Ma3,2,*, Jianxin Shen4, Menghan Li4, Baoke Hou2, Ming Gao2, Shuijun Zhang1 and Jie Wu1,2,3,4
1Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2Department of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
3Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, China
4Department of Physiology, Shantou University Medical College, Shantou, China
*These authors have contributed equally to this work
Jie Wu, email: [email protected]
Keywords: 2-aminoethoxydiphenyl borate, store-operated Ca2+ entry (SOCE), DPB161, Ca2+ oscillations, rat submandibular cells
Received: February 04, 2017 Accepted: May 06, 2017 Published: June 27, 2017
Cellular Ca2+ signals play a critical role in cell physiology and pathology. In most non-excitable cells, store-operated Ca2+ entry (SOCE) is an important mechanism by which intracellular Ca2+ signaling is regulated. However, few drugs can selectively modulate SOCE. 2-Aminoethoxydiphenyl borate (2APB) and its analogs (DPB162 and DPB163) have been reported to inhibit SOCE. Here, we examined the effects of another 2-APB analog, DPB161 on SOCE in acutely-isolated rat submandibular cells. Both patch-clamp recordings and Ca2+ imaging showed that upon removal of extracellular Ca2+ ([Ca2+]o=0), rat submandibular cells were unable to maintain ACh-induced Ca2+ oscillations, but restoration of [Ca2+]o to refill Ca2+ stores enable recovery of these Ca2+ oscillations. However, addition of 50 μM DPB161 with [Ca2+]o to extracellular solution prevented the refilling of Ca2+ store. Fura-2 Ca2+ imaging showed that DPB161 inhibited SOCE in a concentration-dependent manner. After depleting Ca2+ stores by thapsigargin treatment, bath perfusion of 1 mM Ca2+ induced [Ca2+]i elevation in a manner that was prevented by DPB161. Collectively, these results show that the 2-APB analog DPB161 blocks SOCE in rat submandibular cells, suggesting that this compound can be developed as a pharmacological tool for the study of SOCE function and as a new therapeutic agent for treating SOCE-associated disorders.
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