Cytoplasmic free calcium, myosin light chain phosphorylation, and force in phasic and tonic smooth muscle.

Himpens, Bernard; Matthijs, Gert; Somlyo, Andrew P.; Butler, Thomas M.

doi:10.1085/jgp.92.6.713

Cited by 143 publications

(63 citation statements)

References 37 publications

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“…In the presence of high K+, MLC phosphorylation transiently increased and then decreased to a level near the resting level. This result is similar to the observation by Himpens et al (29). Our results showed that Li+ inhibited the high K+-induced increase in MLC phosphorylation.…”

Section: Permeabilized Musclesupporting

confidence: 93%

The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

Hori

Shimizu

Nakajyo

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-The mechanism of the inhibitory effect of Li+ on contraction was examined in guinea pig ileal longitudinal smooth muscle. Li+-substitution (68.4 mM) reversed contractions induced by high K+ (45.4 mM), carbachol (1 teM) and histamine (1 tM) without changing the cytosolic Ca" level. Li+ also had no effect on the increase in 45Ca2+ uptake stimulated by high K+. High K+ transiently increased myosin light chain (MLC) phosphorylation, reaching a peak at 6-9 sec. Li+-substitution inhibited the high K+-induced MLC phosphorylation. In permeabilized ileal strips, contraction induced by 1 1iM Ca 2+ was inhibited by 10 mM Lit The inhibitory effect was antagonized by increasing the concentration of Ca 2+ or calmodulin. In the permeabilized muscle in which MLC was previously thiophosphorylated with 1 mM ATPIS and 3 PM Ca2+, ATP induced contraction in Ca 21 free buffer. Li+ added during this contraction did not show an inhibitory effect. In contrast, when 30 mM Li+ was added during the thiophosphorylation, the contraction induced by the subsequent addition of ATP was inhibited. Li+ (30 mM) changed neither the rate of relaxation induced by removing external Ca 21 in permeabilized muscle nor the rate of dephosphorylation of MLC induced by crude phosphatase extracted from the ileum. Li+ (15 mM), on the other hand, inhibited the rate of phosphorylation of MLC caused by crude MLC kinase extracted from the ileum. Li+ did not inhibit the calmodulin activity as measured with the (Ca 2+ + Mg2+)-ATPase activity of the erythrocyte membrane. These results suggest that the inhibitory effect of Li+ on contractions is attributable to the inhibition of MLC kinase in guinea pig ileum. Keywords: Li+ (lithium ion), Smooth muscle (intestine), Contractile element, Myosin light chain kinase, Cytosolic Ca 2+ levelLi+ has been shown to have various biological actions such as inhibition of phosphatidylinositol turnover (1, 2) and adenylate cyclase (3, 4). In intestinal smooth muscle, Li+ relaxes contractions induced by high concentrations of KCl and receptor agonists (5 -7). Treatment of guinea pig ileal muscle with 68.4 mM Li+ solution increased the cellular Li+ content to 10-20 mmol/kg wet wt. in 30-60 min (8) and the inhibitory effect increased with the accumulation of Li+ in the cell (9-11). Recently, we have reported that Li+-induced relaxation is not due to a decrease in cytosolic Ca 2+ level ([Ca2+];) and that Li+ relaxes Ca 2+-induced contraction in permeabilized tissue (11). The purpose of the present experiments is to further clarify the mechanism for the inhibitory effect of Li+ in guinea pig ileal smooth muscle. Preparations and solutionsIleum was isolated from male guinea pigs (300 -400 g) after stunning by a sharp blow on the neck and exsanguination. Longitudinal smooth muscle strips, approximately 5-mm-wide and 10-mm-long, were prepared. Normal physiological salt solution (PSS) contained: 136.9 mM NaCl, 5.4 mM KCI, 1.5 mM CaC12, 1.0 MM MgC12, 23.8 mM NaHCO3 and 5.5 mM glucose. High K+ solutions were made by hyperosmotically add...

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Section: Permeabilized Musclesupporting

confidence: 93%

The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

Hori

Shimizu

Nakajyo

et al. 1995

Japanese Journal of Pharmacology

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“…In summary, this study presents evidence that rapid increases in [Ca 2ϩ ] i in smooth muscle (13,25,35) induced by the stimulus, KCl, activates two distinct, temporally separated events: 1) the well-established activation of MLC kinase causing rapid, strong increases in MLC phosphorylation and cross-bridge cycling, producing a peak contraction (5,13,33), and 2) Ca 2ϩ -calmodulin-activated increases in ROK translocation to caveolae, leading to maintenance of tonic force (shown here). In conclusion, these data support the hypothesis that any stimulus that increases [Ca 2ϩ ] i in arterial muscle will cause increased ROK translocation to caveolae at the cell periphery, where additional signaling events, such as activation of ZIP-like kinase (20), that lead to sustained MLC phosphorylation and force in the face of temporally falling [Ca 2ϩ ] i may be coordinated.…”

Section: Effect Of Nifedipine and Tfp On The Ability Of Kclmentioning

confidence: 52%

K+ depolarization induces RhoA kinase translocation to caveolae and Ca²⁺ sensitization of arterial muscle

Urban

Berg

Ratz

2003

American Journal of Physiology-Cell Physiology

102

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KCl causes smooth muscle contraction by elevating intracellular free Ca2+, whereas receptor stimulation activates an additional mechanism, termed Ca2+ sensitization, that can involve activation of RhoA-associated kinase (ROK) and PKC. However, recent studies support the hypothesis that KCl may also increase Ca2+ sensitivity. Our data showed that the PKC inhibitor GF-109203X did not, whereas the ROK inhibitor Y-27632 did, inhibit KCl-induced tonic (5 min) force and myosin light chain (MLC) phosphorylation in rabbit artery. Y-27632 also inhibited BAY K 8644- and ionomycin-induced MLC phosphorylation and force but did not inhibit KCl-induced Ca2+ entry or peak (∼15 s) force. Moreover, KCl and BAY K 8644 nearly doubled the amount of ROK colocalized to caveolae at 30 s, a time that preceded inhibition of force by Y-27632. Colocalization was not inhibited by Y-27632 but was abolished by nifedipine and the calmodulin blocker trifluoperazine. These data support the hypothesis that KCl caused Ca2+ sensitization via ROK activation. We discuss a novel model for ROK activation involving translocation to caveolae that is dependent on Ca2+ entry and involves Ca2+-calmodulin activation.

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“…Elevated intracellular calcium (Ca i 2ϩ ) levels stimulate smooth muscle contraction (17), and Ca o 2ϩ is required for the maintenance of myogenic tone (14), the intrinsic contractile activity of arterial wall smooth muscle that represents an important determinant of vascular resistance. The response to Ca o 2ϩ varies between artery type with some tissues showing contraction and others relaxation (3, 22, 35, 49 -51), but, in either case, these studies demonstrate that arteries can sense changes in [Ca 2ϩ ] o .…”

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confidence: 99%

Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

Ohanian¹,

Gatfield²,

Ward³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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), and, recently, a receptor that senses changes in Ca 2ϩ , the calcium-sensing receptor (CaR), has been detected in vascular tissue. We investigated whether the CaR is involved in the regulation of myogenic tone in rat subcutaneous small arteries. Immunoblot analysis using a monoclonal antibody against the CaR demonstrated its presence in rat subcutaneous arteries. To determine whether the CaR was functionally active, segments of artery (Ͻ250 m internal diameter) mounted in a pressure myograph with an intraluminal pressure of 70 mmHg were studied after the development of myogenic tone. Increasing Ca o 2ϩ concentration ([Ca 2ϩ ]o) cumulatively from 0.5 to 10 mM induced an initial constriction (0.5-2 mM) followed by dilation (42 Ϯ 5% loss of tone). The dose-dependent dilation was mimicked by other known CaR agonists including magnesium (1-10 mM) and the aminoglycosides neomycin (0.003-10 mM) and kanamycin (0.003-3 mM). PKC activation with the phorbol ester phorbol-12,13-dibutyrate (20nM) inhibited the dilation induced by high [Ca 2ϩ ]o or neomycin, whereas inhibition of PKC with GF109203X (10 M) increased the responses to Ca o 2ϩ or neomycin, consistent with the role of PKC as a negative regulator of the CaR. We conclude that rat subcutaneous arteries express a functionally active CaR that may be involved in the modulation of myogenic tone and hence the regulation of peripheral vascular resistance. vascular smooth muscle; magnesium; aminoglycosides; contractility; peripheral vascular resistance THE EXTRACELLULAR CALCIUM-SENSING RECEPTOR (CaR) is a G protein-coupled receptor capable of sensing changes in extracellular calcium (Ca o 2ϩ ) concentration ([Ca 2ϩ ] o ). Primarily, the CaR regulates calcium homeostasis by suppressing parathyroid hormone secretion and renal Ca 2ϩ reabsorption. In addition, the CaR is also expressed in tissues and cell types outside the calcium homeostatic system including neural and cardiovascular tissues [reviewed by Brown and Macleod (8)]. However, the functional significance of the receptor in these noncalcium homeostatic tissues remains unclear.Calcium is an important regulator of contractility. Elevated intracellular calcium (Ca i 2ϩ ) levels stimulate smooth muscle contraction (17), and Ca o 2ϩ is required for the maintenance of myogenic tone (14), the intrinsic contractile activity of arterial wall smooth muscle that represents an important determinant of vascular resistance. The response to Ca o 2ϩ varies between artery type with some tissues showing contraction and others relaxation (3, 22, 35, 49 -51), but, in either case, these studies demonstrate that arteries can sense changes in [Ca 2ϩ ] o . In this regard, CaR expression has been reported in the perivascular sensory nerves of rat small mesenteric (10), basilar, renal, and coronary arteries (43). Increasing [Ca 2ϩ ] o (1.25-5 mM) induced a concentration-dependent relaxation of rat small mesenteric arteries precontracted with norepinephrine that was dependent on intact perivascular nerves (10,34,44) and associated...

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Cytoplasmic free calcium, myosin light chain phosphorylation, and force in phasic and tonic smooth muscle.

Cited by 143 publications

References 37 publications

The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

K+ depolarization induces RhoA kinase translocation to caveolae and Ca²⁺ sensitization of arterial muscle

Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

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Cytoplasmic free calcium, myosin light chain phosphorylation, and force in phasic and tonic smooth muscle.

Cited by 143 publications

References 37 publications

The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

K+ depolarization induces RhoA kinase translocation to caveolae and Ca2+ sensitization of arterial muscle

Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

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K+ depolarization induces RhoA kinase translocation to caveolae and Ca²⁺ sensitization of arterial muscle