Pulmonary vasoconstriction and vascular medial hypertrophy greatly contribute to the elevated pulmonary vascular resistance in patients with pulmonary hypertension. A rise in cytosolic free Ca²⁺ ([Ca²⁺]_cyt) in pulmonary artery smooth muscle cells (PASMC) triggers vasoconstriction and stimulates cell growth. Membrane potential (E _m) regulates [Ca²⁺]_cyt by governing Ca²⁺influx through voltage-dependent Ca²⁺ channels. Thus intracellular Ca²⁺ may serve as a shared signal transduction element that leads to pulmonary vasoconstriction and vascular remodeling. In PASMC, activity of voltage-gated K⁺(Kv) channels regulates resting E _m. In this study, we investigated whether changes of Kv currents [I _K(V)], E _m, and [Ca²⁺]_cyt affect cell growth by comparing these parameters in proliferating and growth-arrested PASMC. Serum deprivation induced growth arrest of PASMC, whereas chelation of extracellular Ca²⁺ abolished PASMC growth. Resting [Ca²⁺]_cyt was significantly higher, and resting E _m was more depolarized, in proliferating PASMC than in growth-arrested cells. Consistently, whole cell I _K(V) was significantly attenuated in PASMC during proliferation. Furthermore, E _mdepolarization significantly increased resting [Ca²⁺]_cyt and augmented agonist-mediated rises in [Ca²⁺]_cyt in the absence of extracellular Ca²⁺. These results demonstrate that reducedI _K(V), depolarized E _m, and elevated [Ca²⁺]_cyt may play a critical role in stimulating PASMC proliferation. Pulmonary vascular medial hypertrophy in patients with pulmonary hypertension may be partly caused by a membrane depolarization-mediated increase in [Ca²⁺]_cyt in PASMC.