Pulmonary arterial hypertension (PAH) is a rare and fatal disease of the pulmonary artery. The major pathogenesis is sustained vasoconstriction and vascular remodeling of the pulmonary artery. The vascular remodeling is caused by the enhanced proliferation and reduced apoptosis of pulmonary arterial smooth muscle cells (PASMCs). In the present study, the functional expression of two-pore domain K⁺ (K_2P) channels (KCNK family) was examined in PASMCs from normal subjects and idiopathic pulmonary arterial hypertension (IPAH) patients. Expression analyses revealed that the expressions of KCNK1 (TWIK1) and KCNK2 (TREK1) channels were upregulated in IPAH-PASMCs, whereas those of KCNK3 (TASK1) and KCNK6 (TWIK2) channels were downregulated. The proliferative rate of IPAH-PASMCs was higher than that of normal-PASMCs. The excessive proliferation of IPAH-PASMCs was inhibited by K_2P channel blockers, quinine and tetrapentylammonium (TPA). TPA-induced membrane depolarization was smaller in IPAH-PASMCs than normal-PASMCs. In addition, the excessive proliferation of IPAH-PASMCs was attenuated by siRNA knockdown of KCNK1 (TWIK1) or KCNK2 (TREK1). Taken together, these results suggest that upregulated KCNK1 (TWIK1) and KCNK2 (TREK1) channels facilitate the PASMC proliferation, leading to the development of PAH.