TY - JOUR
T1 - Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation
AU - Platoshyn, Oleksandr
AU - Golovina, Vera A.
AU - Bailey, Colleen L.
AU - Limsuwan, Alisa
AU - Krick, Stefanie
AU - Juhaszova, Magdalena
AU - Seiden, Jan E.
AU - Rubin, Lewis J.
AU - Yuan, Jason X.J.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Intracellular calcium
KW - Membrane potential
KW - Voltage-gated potassium channels
UR - http://www.scopus.com/inward/record.url?scp=0033679957&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033679957&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.2000.279.5.c1540
DO - 10.1152/ajpcell.2000.279.5.c1540
M3 - Article
C2 - 11029301
AN - SCOPUS:0033679957
VL - 279
SP - C1540-C1549
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 5 48-5
ER -