Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation

Oleksandr Platoshyn, Vera A. Golovina, Colleen L. Bailey, Alisa Limsuwan, Stefanie Krick, Magdalena Juhaszova, Jan E. Seiden, Lewis J. Rubin, Jason X.J. Yuan

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

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(m) depolarization significantly increased resting [Ca2+](cyt) and augmented agonist-mediated rises in [Ca2+](cyt) in the absence of extracellular Ca2+. These results demonstrate that reduced I(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.

Original languageEnglish (US)
Pages (from-to)C1540-C1549
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number5 48-5
StatePublished - Dec 7 2000
Externally publishedYes

Keywords

  • Intracellular calcium
  • Membrane potential
  • Voltage-gated potassium channels

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation'. Together they form a unique fingerprint.

  • Cite this

    Platoshyn, O., Golovina, V. A., Bailey, C. L., Limsuwan, A., Krick, S., Juhaszova, M., Seiden, J. E., Rubin, L. J., & Yuan, J. X. J. (2000). Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation. American Journal of Physiology - Cell Physiology, 279(5 48-5), C1540-C1549.