Nonselective cation channel function in sheep pulmonary arteries is affected by postnatal maturation and chronic hypoxia

Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics.

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TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node cells

Cardiovascular Research ◽

10.1016/j.cardiores.2006.11.023 ◽

2007 ◽

Vol 73 (3) ◽

pp. 531-538 ◽

Cited By ~ 111

Author(s):

M DEMION ◽

P BOIS ◽

P LAUNAY ◽

R GUINAMARD

Keyword(s):

Cation Channel ◽

Nonselective Cation Channel

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Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00178.2006 ◽

2007 ◽

Vol 292 (3) ◽

pp. L678-L684 ◽

Cited By ~ 60

Author(s):

Yuansheng Gao ◽

Ada D. Portugal ◽

Sewite Negash ◽

Weilin Zhou ◽

Lawrence D. Longo ◽

...

Keyword(s):

High Altitude ◽

Chronic Hypoxia ◽

Pulmonary Arteries ◽

Regulatory Subunit ◽

Fourth Generation ◽

Minor Effect ◽

Altitude Hypoxia ◽

High Altitude Hypoxia ◽

Rock Activity

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses (∼140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for ∼110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.

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Combined influence of ontogeny and chronic hypoxia on ryanodine receptor function in sheep pulmonary arteries and myocytes

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.1034.8 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

Scott Hadley ◽

Quintin Blood ◽

Peterson Le ◽

Demosthenes G Papamatheakis ◽

Lawrence D Longo ◽

...

Keyword(s):

Ryanodine Receptor ◽

Chronic Hypoxia ◽

Pulmonary Arteries ◽

Receptor Function

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Functional Coupling between Sulfonylurea Receptor Type 1 and a Nonselective Cation Channel in Reactive Astrocytes from Adult Rat Brain

Journal of Neuroscience ◽

10.1523/jneurosci.23-24-08568.2003 ◽

2003 ◽

Vol 23 (24) ◽

pp. 8568-8577 ◽

Cited By ~ 107

Author(s):

Mingkui Chen ◽

Yafeng Dong ◽

J. Marc Simard

Keyword(s):

Rat Brain ◽

Reactive Astrocytes ◽

Cation Channel ◽

Receptor Type ◽

Functional Coupling ◽

Sulfonylurea Receptor ◽

Nonselective Cation Channel ◽

Adult Rat ◽

Adult Rat Brain

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Ca(2+)-activated nonselective cation channel in apical membrane of vestibular dark cells

AJP Cell Physiology ◽

10.1152/ajpcell.1992.262.6.c1423 ◽

1992 ◽

Vol 262 (6) ◽

pp. C1423-C1429 ◽

Cited By ~ 28

Author(s):

D. C. Marcus ◽

S. Takeuchi ◽

P. Wangemann

Keyword(s):

Single Channel ◽

Apical Membrane ◽

Cation Channel ◽

Nonselective Cation Channel ◽

Channel Activity ◽

Dark Cells ◽

Linear Current ◽

Current Voltage ◽

K Secretion ◽

Vestibular Dark Cells

Patch-clamp recordings were made on cell-attached and excised apical membrane from dark cells of the semicircular canal of the gerbil. These cells are thought to secrete K+ and absorb Na+ from the luminal fluid (endolymph). Single-channel events were identified as being equally conductive (27.6 +/- 0.4 pS; n = 48) for K+, Na+, Rb+, Li+, and Cs+ and 1.4 times more permeable to NH4+ but not permeable to Cl-, Ca2+, Ba2+, nor to N-methyl-D-glucamine. The channels displayed linear current-voltage relations that passed nearly through the origin (intercept: -2.6 +/- 0.5 mV; n = 48) when conductive monovalent cations were present on both sides of the membrane in equal concentrations. Channel activity required the presence of Ca2+ at the cytosolic face; there was no activity at less than or equal to 10(-7) M Ca2+ and full activity at greater than or equal to 10(-5) M Ca2+. Cell-attached recordings had a mean reversal voltage of -36.4 +/- 7.9 mV (n = 7), which was interpreted to reflect the intracellular potential of dark cells under the present conditions. We have identified a nonselective cation channel in the apical membrane of vestibular dark cells that might participate in K+ secretion or Na+ absorption under stimulated conditions, but the density appears to be insufficient to fully account for the transepithelial K+ flux.

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