ACID SENSING ION CHANNELS CONTRIBUTE TO HYPOXIA-INDUCED MIGRATION IN HUMAN PULMONARY ARTERIAL SMOOTH MUSCLE CELLS
Tracylyn Yellowhair, Carlos Nitta, Lindsay Herbert, Nikki Jernigan.
University of New Mexico Health Sciences Center, Albuquerque, NM.
Our laboratory has recently shown that acid sensing ion channel 1 (ASIC1) contributes to the arterial remodeling associated with chronic hypoxia-induced pulmonary hypertension. This is consistent with the reported involvement of ASIC in migration, proliferation, and apoptosis in a variety of cells types. However, the contribution of ASIC to hypoxia-induced migration, proliferation, and apoptosis has not been examined. Therefore, we hypothesize that ASIC1 and ASIC3 contribute to hypoxia-induced migration in human pulmonary arterial smooth muscle cells (hPASMC). To test this hypothesis, hPASMC were grown to confluence and placed into basal media 24 h prior to executing an in vitro scratch assay. Following the scratch, hPASMC were treated with the non-selective ASIC inhibitor amiloride, the specific ASIC1 inhibitor psalmotoxin 1, the specific ASIC3 inhibitor APETx2, or vehicle and were then exposed to normoxia (21% oxygen, 5% CO2) or hypoxia (2% oxygen, 5% CO2) for 12 h. Inhibition of ASIC1 and ASIC3 did not alter migration of hPASMC exposed to normoxia, but prevented the hypoxia-induced migration. This data demonstrates that ASIC1 and ASIC3 contribute to hypoxia-induced migration in hPASMCs and describes a potential mechanism in which ASIC contributes to pulmonary arterial remodeling. We will further examine the specific role of ASIC1 and ASIC3 in hypoxia-induced proliferation and apoptosis.