Abstract
Background - Activity of voltage-gated K+ (Kv) channels controls membrane potential (Em) that regulates cytosolic free Ca2+ concentration ([Ca2+]cyt) by regulating voltage-dependent Ca2+ channel function. A rise in [Ca2+]cyt in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a transcription factor that stimulates cell proliferation, affects Kv channel activity in PASMCs was investigated. Methods and Results - Infection of primary cultured PASMCs with an adenoviral vector expressing c-jun increased the protein level of c-Jun and reduced Kv currents (IK(V)) compared with control cells (infected with an empty adenovirus). Using single-cell reverse transcription-polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the current density of IK(V) were both attenuated in c-jun-infected PASMCs compared with control cells and cells infected with antisense c-jun. Overexpression of c-Jun also upregulated protein expression of Kvβ2 and accelerated IK(V) inactivation. Furthermore. Em was more depolarized and [3H]thymidine incorporation was greater in PASMCs infected with c-jun than in control cells and cells infected with antisense c-jun. Conclusions - These results suggest that c-Jun-mediated PASMC proliferation is associated with a decrease in IK(V). The resultant membrane depolarization increases [Ca2+]cyt and enhances PASMC growth.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1557-1563 |
| Number of pages | 7 |
| Journal | Circulation |
| Volume | 104 |
| Issue number | 13 |
| State | Published - Sep 25 2001 |
| Externally published | Yes |
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Keywords
- Genes
- Ion channels
- Lung
- Remodeling
- Transcription factors
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
c-Jun decreases voltage-gated K+ channel activity in pulmonary artery smooth muscle cells. / Yu, Y.; Platoshyn, O.; Zhang, J.; Krick, S.; Zhao, Y.; Rubin, L. J.; Rothman, A.; Yuan, Jason.
In: Circulation, Vol. 104, No. 13, 25.09.2001, p. 1557-1563.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - c-Jun decreases voltage-gated K+ channel activity in pulmonary artery smooth muscle cells
AU - Yu, Y.
AU - Platoshyn, O.
AU - Zhang, J.
AU - Krick, S.
AU - Zhao, Y.
AU - Rubin, L. J.
AU - Rothman, A.
AU - Yuan, Jason
PY - 2001/9/25
Y1 - 2001/9/25
N2 - Background - Activity of voltage-gated K+ (Kv) channels controls membrane potential (Em) that regulates cytosolic free Ca2+ concentration ([Ca2+]cyt) by regulating voltage-dependent Ca2+ channel function. A rise in [Ca2+]cyt in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a transcription factor that stimulates cell proliferation, affects Kv channel activity in PASMCs was investigated. Methods and Results - Infection of primary cultured PASMCs with an adenoviral vector expressing c-jun increased the protein level of c-Jun and reduced Kv currents (IK(V)) compared with control cells (infected with an empty adenovirus). Using single-cell reverse transcription-polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the current density of IK(V) were both attenuated in c-jun-infected PASMCs compared with control cells and cells infected with antisense c-jun. Overexpression of c-Jun also upregulated protein expression of Kvβ2 and accelerated IK(V) inactivation. Furthermore. Em was more depolarized and [3H]thymidine incorporation was greater in PASMCs infected with c-jun than in control cells and cells infected with antisense c-jun. Conclusions - These results suggest that c-Jun-mediated PASMC proliferation is associated with a decrease in IK(V). The resultant membrane depolarization increases [Ca2+]cyt and enhances PASMC growth.
AB - Background - Activity of voltage-gated K+ (Kv) channels controls membrane potential (Em) that regulates cytosolic free Ca2+ concentration ([Ca2+]cyt) by regulating voltage-dependent Ca2+ channel function. A rise in [Ca2+]cyt in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a transcription factor that stimulates cell proliferation, affects Kv channel activity in PASMCs was investigated. Methods and Results - Infection of primary cultured PASMCs with an adenoviral vector expressing c-jun increased the protein level of c-Jun and reduced Kv currents (IK(V)) compared with control cells (infected with an empty adenovirus). Using single-cell reverse transcription-polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the current density of IK(V) were both attenuated in c-jun-infected PASMCs compared with control cells and cells infected with antisense c-jun. Overexpression of c-Jun also upregulated protein expression of Kvβ2 and accelerated IK(V) inactivation. Furthermore. Em was more depolarized and [3H]thymidine incorporation was greater in PASMCs infected with c-jun than in control cells and cells infected with antisense c-jun. Conclusions - These results suggest that c-Jun-mediated PASMC proliferation is associated with a decrease in IK(V). The resultant membrane depolarization increases [Ca2+]cyt and enhances PASMC growth.
KW - Genes
KW - Ion channels
KW - Lung
KW - Remodeling
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=0035949526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035949526&partnerID=8YFLogxK
M3 - Article
VL - 104
SP - 1557
EP - 1563
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 13
ER -