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The contraction of smooth muscle cells of intrapulmonary arterioles is determined by the frequency of Ca2+ oscillations induced by 5-HT and KCl.

Perez JF, Sanderson MJ - J. Gen. Physiol. (2005)

Bottom Line: Increased resistance of the small blood vessels within the lungs is associated with pulmonary hypertension and results from a decrease in size induced by the contraction of their smooth muscle cells (SMCs).Increasing concentrations of extracellular KCl induced transient contractions in the SMCs and a reduction in the arteriole luminal size. 5-HT induced oscillations in [Ca(2+)](i) within the SMCs, and the frequency of these Ca(2+) oscillations was dependent on the agonist concentration and correlated with the extent of sustained arteriole contraction.By contrast, KCl induced Ca(2+) oscillations that occurred with low frequencies and were preceded by small, localized transient Ca(2+) events.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

ABSTRACT
Increased resistance of the small blood vessels within the lungs is associated with pulmonary hypertension and results from a decrease in size induced by the contraction of their smooth muscle cells (SMCs). To study the mechanisms that regulate the contraction of intrapulmonary arteriole SMCs, the contractile and Ca(2+) responses of the arteriole SMCs to 5-hydroxytrypamine (5-HT) and KCl were observed with phase-contrast and scanning confocal microscopy in thin lung slices cut from mouse lungs stiffened with agarose and gelatin. 5-HT induced a concentration-dependent contraction of the arterioles. Increasing concentrations of extracellular KCl induced transient contractions in the SMCs and a reduction in the arteriole luminal size. 5-HT induced oscillations in [Ca(2+)](i) within the SMCs, and the frequency of these Ca(2+) oscillations was dependent on the agonist concentration and correlated with the extent of sustained arteriole contraction. By contrast, KCl induced Ca(2+) oscillations that occurred with low frequencies and were preceded by small, localized transient Ca(2+) events. The 5-HT-induced Ca(2+) oscillations and contractions occurred in the absence of extracellular Ca(2+) and were resistant to Ni(2+) and nifedipine but were abolished by caffeine. KCl-induced Ca(2+) oscillations and contractions were abolished by the absence of extracellular Ca(2+) and the presence of Ni(2+), nifedipine, and caffeine. Arteriole contraction was induced or abolished by a 5-HT(2)-specific agonist or antagonist, respectively. These results indicate that 5-HT, acting via 5-HT(2) receptors, induces arteriole contraction by initiating Ca(2+) oscillations and that KCl induces contraction via Ca(2+) transients resulting from the overfilling of internal Ca(2+) stores. We hypothesize that the magnitude of the sustained intrapulmonary SMC contraction is determined by the frequency of Ca(2+) oscillations and also by the relaxation rate of the SMC.

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Concentration dependence of 5-HT–induced Ca2+ signaling in arteriole SMCs. Different lung slices were stimulated with different concentrations of 5-HT as indicated by the bars. (A–C) Representative changes in fluorescence in defined ROIs over individual SMCs for each concentration. Increases in 5-HT concentration induced increases in the frequency of Ca2+ oscillations. (D–F) Line-scan plots showing the responses to different concentrations of 5-HT in adjacent SMCs. (G) The mean frequency of Ca2+ oscillations induced in arteriole SMCs by 5-HT; mean ± SEM of at least seven cells from slices from three mice. **, P < 0.01 between all concentrations (Student's t test).
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fig4: Concentration dependence of 5-HT–induced Ca2+ signaling in arteriole SMCs. Different lung slices were stimulated with different concentrations of 5-HT as indicated by the bars. (A–C) Representative changes in fluorescence in defined ROIs over individual SMCs for each concentration. Increases in 5-HT concentration induced increases in the frequency of Ca2+ oscillations. (D–F) Line-scan plots showing the responses to different concentrations of 5-HT in adjacent SMCs. (G) The mean frequency of Ca2+ oscillations induced in arteriole SMCs by 5-HT; mean ± SEM of at least seven cells from slices from three mice. **, P < 0.01 between all concentrations (Student's t test).

Mentions: In the range of 0.01 to 1 μM, 5-HT induced a concentration-dependent increase in the frequency of the Ca2+ oscillations in arteriole SMCs (Fig. 4). At 0.01 μM, 5-HT induced a frequency of 0.6 ± 0.2 cycles min−1 (n = 7 cells from 3 slices from 2 mice) while at 1 μM, 5-HT induced a frequency of 6 ± 0.5 cycles min−1 (n = 13 cells from 6 slices from 3 mice) (Fig. 4 G).


The contraction of smooth muscle cells of intrapulmonary arterioles is determined by the frequency of Ca2+ oscillations induced by 5-HT and KCl.

Perez JF, Sanderson MJ - J. Gen. Physiol. (2005)

Concentration dependence of 5-HT–induced Ca2+ signaling in arteriole SMCs. Different lung slices were stimulated with different concentrations of 5-HT as indicated by the bars. (A–C) Representative changes in fluorescence in defined ROIs over individual SMCs for each concentration. Increases in 5-HT concentration induced increases in the frequency of Ca2+ oscillations. (D–F) Line-scan plots showing the responses to different concentrations of 5-HT in adjacent SMCs. (G) The mean frequency of Ca2+ oscillations induced in arteriole SMCs by 5-HT; mean ± SEM of at least seven cells from slices from three mice. **, P < 0.01 between all concentrations (Student's t test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2234075&req=5

fig4: Concentration dependence of 5-HT–induced Ca2+ signaling in arteriole SMCs. Different lung slices were stimulated with different concentrations of 5-HT as indicated by the bars. (A–C) Representative changes in fluorescence in defined ROIs over individual SMCs for each concentration. Increases in 5-HT concentration induced increases in the frequency of Ca2+ oscillations. (D–F) Line-scan plots showing the responses to different concentrations of 5-HT in adjacent SMCs. (G) The mean frequency of Ca2+ oscillations induced in arteriole SMCs by 5-HT; mean ± SEM of at least seven cells from slices from three mice. **, P < 0.01 between all concentrations (Student's t test).
Mentions: In the range of 0.01 to 1 μM, 5-HT induced a concentration-dependent increase in the frequency of the Ca2+ oscillations in arteriole SMCs (Fig. 4). At 0.01 μM, 5-HT induced a frequency of 0.6 ± 0.2 cycles min−1 (n = 7 cells from 3 slices from 2 mice) while at 1 μM, 5-HT induced a frequency of 6 ± 0.5 cycles min−1 (n = 13 cells from 6 slices from 3 mice) (Fig. 4 G).

Bottom Line: Increased resistance of the small blood vessels within the lungs is associated with pulmonary hypertension and results from a decrease in size induced by the contraction of their smooth muscle cells (SMCs).Increasing concentrations of extracellular KCl induced transient contractions in the SMCs and a reduction in the arteriole luminal size. 5-HT induced oscillations in [Ca(2+)](i) within the SMCs, and the frequency of these Ca(2+) oscillations was dependent on the agonist concentration and correlated with the extent of sustained arteriole contraction.By contrast, KCl induced Ca(2+) oscillations that occurred with low frequencies and were preceded by small, localized transient Ca(2+) events.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

ABSTRACT
Increased resistance of the small blood vessels within the lungs is associated with pulmonary hypertension and results from a decrease in size induced by the contraction of their smooth muscle cells (SMCs). To study the mechanisms that regulate the contraction of intrapulmonary arteriole SMCs, the contractile and Ca(2+) responses of the arteriole SMCs to 5-hydroxytrypamine (5-HT) and KCl were observed with phase-contrast and scanning confocal microscopy in thin lung slices cut from mouse lungs stiffened with agarose and gelatin. 5-HT induced a concentration-dependent contraction of the arterioles. Increasing concentrations of extracellular KCl induced transient contractions in the SMCs and a reduction in the arteriole luminal size. 5-HT induced oscillations in [Ca(2+)](i) within the SMCs, and the frequency of these Ca(2+) oscillations was dependent on the agonist concentration and correlated with the extent of sustained arteriole contraction. By contrast, KCl induced Ca(2+) oscillations that occurred with low frequencies and were preceded by small, localized transient Ca(2+) events. The 5-HT-induced Ca(2+) oscillations and contractions occurred in the absence of extracellular Ca(2+) and were resistant to Ni(2+) and nifedipine but were abolished by caffeine. KCl-induced Ca(2+) oscillations and contractions were abolished by the absence of extracellular Ca(2+) and the presence of Ni(2+), nifedipine, and caffeine. Arteriole contraction was induced or abolished by a 5-HT(2)-specific agonist or antagonist, respectively. These results indicate that 5-HT, acting via 5-HT(2) receptors, induces arteriole contraction by initiating Ca(2+) oscillations and that KCl induces contraction via Ca(2+) transients resulting from the overfilling of internal Ca(2+) stores. We hypothesize that the magnitude of the sustained intrapulmonary SMC contraction is determined by the frequency of Ca(2+) oscillations and also by the relaxation rate of the SMC.

Show MeSH
Related in: MedlinePlus