scholarly journals Increased Ca2+ Influx in the Resting State Maintains the Myogenic Tone and Activates Charybdotoxin-Sensitive K+ Channels in Dog Basilar Artery

1993 ◽  
Vol 13 (6) ◽  
pp. 969-977 ◽  
Author(s):  
Masahisa Asano ◽  
Kaoru Masuzawa-Ito ◽  
Tomohiro Matsuda ◽  
Yoshio Suzuki ◽  
Hirofumi Oyama ◽  
...  

We examined whether Ca2+ channel function in the resting state alters the resting tone and Ca2+ -activated K+ (KCa) channel function in dog basilar artery: data were compared with findings in the mesenteric artery. Isolated dog basilar artery maintained a myogenic tone; that is, the resting tone decreased when either the Krebs solution was replaced with a Ca2+ -free solution or nifedipine was added. The basal 45Ca influx in the resting state of the basilar artery was significantly increased compared with that in the mesenteric artery, and this increase in the basilar artery was reduced by nifedipine. The addition of charybdotoxin (ChTX), a blocker of large-conductance KCa channels, to the resting strips caused a concentration-dependent contraction in the basilar artery but not in the mesenteric artery. The ChTX-induced contraction in the basilar artery was abolished by nifedipine. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in the basilar artery than in the mesenteric artery. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in the basilar artery. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of the basilar artery and that the myogenic tone was therefore maintained and the ChTX-sensitive KCa channels were highly activated.

1991 ◽  
Vol 11 (3) ◽  
pp. 371-379 ◽  
Author(s):  
Chiharu Tanoi ◽  
Yoshio Suzuki ◽  
Masato Shibuya ◽  
Kenichiro Sugita ◽  
Kaoru Masuzawa ◽  
...  

Vasoconstrictor effects of endothelin-1 (ET) were investigated in endothelium-denuded strips of cerebral (basilar and posterior cerebral) and mesenteric arteries of the dog. ET produced a concentration-dependent contraction in these arteries. Contractile responses to lower concentrations (below 3 × 10−10 M) of ET were significantly greater in the cerebral arteries than in the mesenteric artery. Inhibition by nifedipine of the contractile responses to ET was greater in the basilar artery than in the mesenteric artery. After the inhibition by 10−7 M nifedipine, the remaining responses to ET were similar in the two arteries. Cerebral arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a Ca2+ -free solution containing 0.1 m M EGTA (0-Ca solution). Readdition of Ca2+ to the cerebral arteries placed in the 0-Ca solution caused a biphasic contraction that was sensitive to nifedipine. When 10−9 M ET was introduced before the Ca2+-induced contraction, this peptide produced only a very small contraction, but enhanced the Ca2+-induced contraction. The extent of the enhancement induced by ET was much greater in the cerebral arteries than in the mesenteric artery. These results indicate that the enhanced responses to ET in the cerebral arteries were dependent to a large extent on Ca2+ influx through voltage-dependent Ca2+ channels (VDCs). It is likely that the VDCs in these arteries are more activated in the resting state than those in the mesenteric artery.


1993 ◽  
Vol 265 (3) ◽  
pp. H843-H851 ◽  
Author(s):  
M. Asano ◽  
K. Masuzawa-Ito ◽  
T. Matsuda ◽  
Y. Imaizumi ◽  
M. Watanabe ◽  
...  

Carotid arteries from spontaneously hypertensive rats (SHR) exhibited an active tone when exposed to a physiological salt solution; that is, the tension decreased when nifedipine was added. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the resting state of these arteries, the effects of agents that interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid arteries from SHR and normotensive Wistar-Kyoto rats (WKY). The addition of charybdotoxin, a blocker of high-conductance KCa channels, to the resting strips produced a concentration-dependent contraction in SHR but not in WKY. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in SHR than in WKY. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in SHR. The effect of nifedipine on tension and 86Rb efflux in 25.9 mM K(+)-contracted strips of WKY was comparable to the effect of this blocker in the resting strips of SHR. The basal 45Ca influx in resting strips of SHR was significantly increased when compared with WKY, and this increase in SHR was abolished by nifedipine. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of carotid arteries from SHR and that the KCa channels were highly activated.


2015 ◽  
Vol 308 (8) ◽  
pp. C631-C641 ◽  
Author(s):  
Michele Visentin ◽  
Ersin Selcuk Unal ◽  
Mitra Najmi ◽  
Andras Fiser ◽  
Rongbao Zhao ◽  
...  

The proton-coupled folate transporter (PCFT) mediates intestinal folate absorption and transport of folates across the choroid plexus. This study focuses on the role of Tyr residues in PCFT function. The substituted Cys-accessibility method identified four Tyr residues (Y291, Y362, Y315, and Y414) that are accessible to the extracellular compartment; three of these (Y291, Y362, and Y315) are located within or near the folate binding pocket. When the Tyr residues were replaced with Cys or Ala, these mutants showed similar (up to 6-fold) increases in influx Vmax and Kt/ Ki for [3H]methotrexate and [3H]pemetrexed. When the Tyr residues were replaced with Phe, these changes were moderated or absent. When Y315A PCFT was used as representative of the mutants and [3H]pemetrexed as the transport substrate, this substitution did not increase the efflux rate constant. Furthermore, neither influx nor efflux mediated by Y315A PCFT was transstimulated by the presence of substrate in the opposite compartment; however, substantial bidirectional transstimulation of transport was mediated by wild-type PCFT. This resulted in a threefold greater efflux rate constant for cells that express wild-type PCFT than for cells that express Y315 PCFT under exchange conditions. These data suggest that these Tyr residues, possibly through their rigid side chains, secure the carrier in a high-affinity state for its folate substrates. However, this may be achieved at the expense of constraining the carrier's mobility, thereby decreasing the rate at which the protein oscillates between its conformational states. The Vmax generated by these Tyr mutants may be so rapid that further augmentation during transstimulation may not be possible.


1980 ◽  
Vol 59 (s6) ◽  
pp. 195s-197s ◽  
Author(s):  
W. R. Fitzgibbon ◽  
T. O. Morgan ◽  
J. B. Myers

1. The rate constant for total 22Na efflux from erythrocytes was examined in patients with mild to moderate hypertension and in normotensive controls. No difference in 22Na efflux rate constant was found when the cells from both groups were incubated in artificial medium. When the cells from both groups were incubated in their own plasma, the rate constant for Na efflux was significantly elevated for hypertensive patients compared with controls (0.40 ± 0.02, 0.36 ± 0.01 respectively; P<0.05). 2. In hypertensive patients sodium efflux rate constant varied inversely with 24 h urinary sodium excretion when erythrocytes were incubated in artificial medium (r = − 0.34, P<0.05) or in plasma (r = −0.42, P<0.05). No association between sodium efflux rate constant and urinary sodium excretion occurred in normotensive subjects. 3. These findings provide further evidence that sodium is an important aetiological factor in hypertension. In ‘salt-sensitive’ individuals dietary sodium may interact with the regulation of cellular sodium transport via both humoral and cellular mechanisms to elevate blood pressure.


1980 ◽  
Vol 59 (5) ◽  
pp. 353-357 ◽  
Author(s):  
R. B. Jones ◽  
P. J. Hilton ◽  
J. Michael ◽  
J. Patrick ◽  
V. E. Johnson

1. The transport of zinc has been studied in normal human leucocytes incubated in both a tissue culture medium and Krebs buffer. 2. 65Zn influx is characterized by an initial rapid phase followed by a slower influx. 65Zn influx is directly dependent upon the extracellular zinc concentration. 3. Net zinc influx could only be demonstrated in Krebs buffer at zinc concentrations in excess of 4.3 μmol/l and in tissue culture fluid at zinc concentrations in excess of 43.1 μmol/l. 4. A 65Zn efflux rate constant of approximately 1.0 per h was observed in both 4.3 and 15.4 μmol of zinc/l of Krebs buffer or tissue culture fluid. 5. In a zero external zinc Krebs buffer the 65Zn efflux rate constant fell to 0.57 per h and was accompanied by a small net zinc efflux.


1988 ◽  
Vol 75 (6) ◽  
pp. 577-579 ◽  
Author(s):  
J. F. Morris ◽  
L. Poston ◽  
C. D. Wolfe ◽  
P. J. Hilton

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured by radioimmunoassay for digoxin in 13 paired samples of arterial and venous umbilical cord serum. EDLI was present in vein and artery, but was higher in the venous samples (P < 0.025). 2. The venous cord serum inhibited the ouabain-sensitive sodium efflux rate constant of a normal mixed leucocyte population when compared with the effect of arterial cord serum (P < 0.005). 3. It is suggested that the placenta may be involved in the production or metabolism of neonatal EDLI and of the inhibitor of sodium transport.


1995 ◽  
Vol 198 (1) ◽  
pp. 227-233 ◽  
Author(s):  
P Croghan ◽  
J Noble-Nesbitt ◽  
A Appel

A method is described for investigating the rate of loss of water and carbon dioxide from terrestrial insects by absorbing tritiated water and 14CO2 from a gas stream flowing past the insect. The loss of water and carbon dioxide can be studied simultaneously with a time resolution (nominal) down to 2 min. The theoretical and experimental bases of analysing the data are considered in detail. The determination of the efflux rate constant for water is straightforward and, if an estimate of surface area is available, the efflux rate constant can be converted to a permeability coefficient. In the case of 14CO2 loss, the interpretation is complicated by the presence of other compartments within the body that can be labelled with 14C. A multicompartment model of 14C exchange is developed and a method of obtaining the efflux rate constant of 14CO2 is described. The efflux rate constant for 14CO2 can be used to estimate CO2 output.


1984 ◽  
Vol 66 (3) ◽  
pp. 365-368
Author(s):  
Kevin Morgan ◽  
M. Afzal Mir

1. Previous studies have shown that myeloid leukaemic blast cells contain a heat stable factor which inhibits bidirectional sodium transport in normal erythrocytes. This study was undertaken to establish whether leukaemic promyelocytes in culture secrete this factor. 2. Two cell-lines of leukaemic promyelocytes (HL-60 and JR) were grown and culture media from both reduced significantly the ouabain-insensitive sodium efflux rate constant, whereas conditioned culture medium (incubated like the cells in culture) had no inhibitory effect. 3. Promyelocyte extract reduced significantly (P < 0.01) the total sodium efflux rate constant from 0.393 ± 0.030 (sd) to 0.311 ± 0.060, and ouabain-insensitive efflux rate constant from 0.131 ± 0.008 to 0.079 ± 0.009 (P<0.001). 4. The inhibitory factor was heat stable (80°C for 30 min) and it inhibited sodium efflux through a pathway which was not inhibited by ouabain or frusemide. 5. These studies suggest that leukaemic promyelocytes secrete the previously identified passive sodium transport inhibitory factor.


1983 ◽  
Vol 64 (2) ◽  
pp. 177-182 ◽  
Author(s):  
E. Jill Rubython ◽  
D. B. Morgan

1. The sodium content, the ouabain-sensitive sodium efflux and efflux rate constant and the ouabain-binding capacity were measured in the erythrocytes of 53 patients with hypokalaemia and in 37 healthy controls. The sodium content alone was measured in a further 57 patients with hypokalaemia. 2. In the patients with hypokalaemia there was an increase in the average sodium content of the erythrocytes, which was entirely due to a reduction in the ouabain-sensitive efflux rate constant. 3. The ratio of the ouabain-sensitive efflux rate constant to the number of sodium pumps was decreased in the patients with hypokalaemia, and was directly related to the plasma potassium. 4. Many patients with moderate hypokalaemia had normal erythrocyte sodium and potassium contents and normal ouabain-sensitive efflux rate constant. These patients had an increased number of sodium pumps, which compensated for the inhibitory effect of hypokalaemia on each sodium pump. 5. This increase in the number of sodium pumps was common even in patients who had probably had hypokalaemia for less than 2 weeks. This finding suggests that there are latent sodium pumps within the circulating erythrocytes.


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