Abstract
Activity of voltage-gated K+ channels (K(V)) in pulmonary arterial smooth muscle cells (PASMC) is pivotal in controlling membrane potential, cytoplasmic free Ca2+ concentration ([Ca2+)(cyt)), and pulmonary vasomotor tone. Acute hypoxia selectively inhibits K(V) channels, depolarizes PASMC, raises [Ca2+](cyt), and causes pulmonary vasoconstriction and vascular remodeling. Prolonged hypoxia (24-60 h) decreased significantly the mRNA levels of K(V) channel α subunits, K(V)1.2 and K(V)1.5. Consistently, the protein levels of K(V)1.2 and K(V)1.5 were also decreased significantly by hypoxia (48-72 h). Nevertheless, hypoxia affected negligibly the mRNA levels of K(V) channel β subunits (K(V)β1, K(V)β2, and K(V)β3). The native K+ channels are composed of pore-forming α and auxiliary β subunits. Assembly of K(V) β subunits with α subunits confers rapid inactivation on the slowly or non-inactivating delayed rectifier K(V) channels. K(V) β subunits also function as an open-channel blocker of K(V) channels. Thus, the diminished transcription and expression of K(V) a subunits may reduce the number of K(V) channels and decrease K(V) currents. Unchanged transcription of K(V) β subunits may increase the fraction of the K(V) channel α subunits that are associated with β subunits and further reduce the total K(V) currents. These data demonstrate a novel mechanism by which chronic hypoxia may cause pulmonary vasoconstriction and hypertension.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2347-2353 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 100 |
| Issue number | 9 |
| State | Published - Nov 1 1997 |
| Externally published | Yes |
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Keywords
- α subunits
- β subunits
- K(V)1.2
- K(V)1.5
- Reverse transcription- PCR
- Western blotting
ASJC Scopus subject areas
- Medicine(all)
Cite this
Hypoxia inhibits gene expression of voltage-gated K+ channel α subunits in pulmonary artery smooth muscle cells. / Wang, Jian; Juhaszova, Magdalena; Rubin, Lewis J.; Yuan, Jason.
In: Journal of Clinical Investigation, Vol. 100, No. 9, 01.11.1997, p. 2347-2353.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypoxia inhibits gene expression of voltage-gated K+ channel α subunits in pulmonary artery smooth muscle cells
AU - Wang, Jian
AU - Juhaszova, Magdalena
AU - Rubin, Lewis J.
AU - Yuan, Jason
PY - 1997/11/1
Y1 - 1997/11/1
N2 - Activity of voltage-gated K+ channels (K(V)) in pulmonary arterial smooth muscle cells (PASMC) is pivotal in controlling membrane potential, cytoplasmic free Ca2+ concentration ([Ca2+)(cyt)), and pulmonary vasomotor tone. Acute hypoxia selectively inhibits K(V) channels, depolarizes PASMC, raises [Ca2+](cyt), and causes pulmonary vasoconstriction and vascular remodeling. Prolonged hypoxia (24-60 h) decreased significantly the mRNA levels of K(V) channel α subunits, K(V)1.2 and K(V)1.5. Consistently, the protein levels of K(V)1.2 and K(V)1.5 were also decreased significantly by hypoxia (48-72 h). Nevertheless, hypoxia affected negligibly the mRNA levels of K(V) channel β subunits (K(V)β1, K(V)β2, and K(V)β3). The native K+ channels are composed of pore-forming α and auxiliary β subunits. Assembly of K(V) β subunits with α subunits confers rapid inactivation on the slowly or non-inactivating delayed rectifier K(V) channels. K(V) β subunits also function as an open-channel blocker of K(V) channels. Thus, the diminished transcription and expression of K(V) a subunits may reduce the number of K(V) channels and decrease K(V) currents. Unchanged transcription of K(V) β subunits may increase the fraction of the K(V) channel α subunits that are associated with β subunits and further reduce the total K(V) currents. These data demonstrate a novel mechanism by which chronic hypoxia may cause pulmonary vasoconstriction and hypertension.
AB - Activity of voltage-gated K+ channels (K(V)) in pulmonary arterial smooth muscle cells (PASMC) is pivotal in controlling membrane potential, cytoplasmic free Ca2+ concentration ([Ca2+)(cyt)), and pulmonary vasomotor tone. Acute hypoxia selectively inhibits K(V) channels, depolarizes PASMC, raises [Ca2+](cyt), and causes pulmonary vasoconstriction and vascular remodeling. Prolonged hypoxia (24-60 h) decreased significantly the mRNA levels of K(V) channel α subunits, K(V)1.2 and K(V)1.5. Consistently, the protein levels of K(V)1.2 and K(V)1.5 were also decreased significantly by hypoxia (48-72 h). Nevertheless, hypoxia affected negligibly the mRNA levels of K(V) channel β subunits (K(V)β1, K(V)β2, and K(V)β3). The native K+ channels are composed of pore-forming α and auxiliary β subunits. Assembly of K(V) β subunits with α subunits confers rapid inactivation on the slowly or non-inactivating delayed rectifier K(V) channels. K(V) β subunits also function as an open-channel blocker of K(V) channels. Thus, the diminished transcription and expression of K(V) a subunits may reduce the number of K(V) channels and decrease K(V) currents. Unchanged transcription of K(V) β subunits may increase the fraction of the K(V) channel α subunits that are associated with β subunits and further reduce the total K(V) currents. These data demonstrate a novel mechanism by which chronic hypoxia may cause pulmonary vasoconstriction and hypertension.
KW - α subunits
KW - β subunits
KW - K(V)1.2
KW - K(V)1.5
KW - Reverse transcription- PCR
KW - Western blotting
UR - http://www.scopus.com/inward/record.url?scp=0030685744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030685744&partnerID=8YFLogxK
M3 - Article
VL - 100
SP - 2347
EP - 2353
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 9
ER -