Functional coupling between calcium-sensing receptor and ion channel in pulmonary hypertension

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860068
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Kinjo Gakuin University
• Principal Investigator: YAMAMURA Aya 金城学院大学, 薬学部, 助教 (40633219)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 肺高血圧 / カルシウム感受性受容体 / イオンチャネル / 血管 / 肺動脈 / 平滑筋

Outline of Final Research Achievements

Sustained vasoconstriction and vascular remodeling due to pulmonary arterial smooth muscle cell (PASMC) proliferation are key pathogenic events for idiopathic pulmonary arterial hypertension (IPAH). We have previously shown that calcium-sensing receptor (CaSR) is upregulated in IPAH-PASMCs and contributes to enhanced calcium response. In this study, we examined whether non-selective cation channel is involved in enhanced calcium influx followed by CaSR activation in IPAH-PASMCs. The expression levels of TRPC channel in IPAH-PASMCs were greater than in normal PASMCs. Knockdown of TRPC channel in IPAH-PASMCs with siRNA attenuated the CaSR-mediated calcium increase. In conclusion, the extracellular calcium-induced calcium increase due to functional coupling between CaSR and TRPC channel is a novel pathogenic mechanism contributing to the augmented calcium influx and excessive PASMC proliferation in IPAH patients.

Free Research Field

薬理学