Dynamic Cytosolic Ca2+ and Force Responses to Muscarinic Stimulation in Airway Smooth Muscle

2021 ◽  
Author(s):  
Young-Soo Han ◽  
Philippe F. Delmotte ◽  
Grace M Arteaga ◽  
Gary C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Isometric Force ◽  
Dynamic Properties ◽  
Maximum Force ◽  
Dynamic Nature ◽  
Regulatory Myosin Light Chain ◽  
Static Assessment ◽  
Phase Loop

During agonist stimulation of airway smooth muscle (ASM), agonists such as ACh induce a transient increase in cytosolic Ca2+ concentration ([Ca2+]cyt), which leads to a contractile response (excitation-contraction (E-C) coupling). Previously, the sensitivity of the contractile response of ASM to elevated [Ca2+]cyt (Ca2+ sensitivity) was assessed as the ratio of maximum force to maximum [Ca2+]cyt. However, this static assessment of Ca2+ sensitivity overlooks the dynamic nature of E-C coupling in ASM. In this study, we simultaneously measured [Ca2+]cyt and isometric force responses to three concentrations of ACh (1, 2.6 and 10 μM). Both maximum [Ca2+]cyt and maximum force responses were ACh concentration-dependent, but force increased disproportionately, thereby increasing static Ca2+ sensitivity. The dynamic properties of E-C coupling were assessed in several ways. The temporal delay between the onset of ACh-induced [Ca2+]cyt and onset force responses was not affected by ACh concentration. The rates of rise of the ACh-induced [Ca2+]cyt and force responses increased with increasing ACh concentration. The integral of the phase-loop plot of [Ca2+]cyt and force from onset to steady-state also increased with increasing ACh concentration, whereas the rate of relaxation remained unchanged. Although these results suggest an ACh concentration-dependent increase in the rate of cross-bridge recruitment and in the rate of rise of [Ca2+]cyt, the extent of regulatory myosin light chain (rMLC20) phosphorylation was not dependent on ACh concentration. We conclude that the dynamic properties of [Ca2+]cyt and force responses in ASM are dependent on ACh concentration but reflect more than changes in the extent of rMLC20 phosphorylation.

Specific reaginic antibody IgG1-induced changes of airway smooth muscle cells

1988 ◽  
Vol 65 (2) ◽  
pp. 767-775 ◽  
Author(s):  
M. Souhrada ◽  
J. F. Souhrada
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Isometric Force ◽  
Airway Smooth Muscle Cells ◽  
Base Line ◽  
Dependent Relationship ◽  
Reaginic Antibody ◽  
Induced Changes ◽  
Igg1 Concentration

It was found that 1) an administration of both immunoglobulin G1 (IgG1) or immunized serum caused an immediate depolarization and an increase in the isometric force of airway smooth muscle (ASM) cells, followed by a sustained hyperpolarization and a return of the tone to the base-line values; 2) an IgG1 concentration-dependent relationship was found between a peak depolarization, a peak hyperpolarization, and a peak isometric force; for these events 50% effective dose (ED50) was found to be 0.17, 0.14, and 0.25 microgram/ml of IgG1, respectively; 3) both electrical and contractile responses to ovalbumin of ASM cells sensitized with IgG1 were also dependent on the concentration of IgG1; the ED50 values of this relationship were 0.27 and 0.25 micrograms/ml of IgG1, respectively; 4) amiloride (10(-8) to 10(-5) M) pretreatment and a sodium-deficient environment attenuated sensitized-induced electrical and contractile changes as well as the response of ASM to ovalbumin (0.1%); and 5) pretreatment of ASM with diphenhydramine (10(-5) M) or FPL 55712 (10(-6) M) had no effect on sensitization-induced changes in membrane potential but attenuated electrical and contractile response of ASM to ovalbumin (0.1%).

cGMP modulation of Ca2+sensitivity in airway smooth muscle

1999 ◽  
Vol 276 (1) ◽  
pp. L35-L40 ◽  
Author(s):  
Keith A. Jones ◽  
Gilbert Y. Wong ◽  
Christopher J. Jankowski ◽  
Masaki Akao ◽  
David O. Warner
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Membrane Receptor ◽  
Tracheal Smooth Muscle ◽  
Response Curves ◽  
Smooth Muscle Preparation ◽  
Regulatory Myosin Light Chain ◽  
The Relationship ◽  
Concentration Response Curve

A β-escin-permeabilized canine tracheal smooth muscle preparation was used to test the hypothesis that cGMP decreases Ca2+ sensitivity in airway smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that regulate Ca2+ sensitivity and not by inhibiting Ca2+/calmodulin activation of the contractile proteins. 8-Bromo-cGMP (100 μM) had no effect on the free Ca2+concentration-response curves generated in the absence of muscarinic receptor stimulation. In the presence of 100 μM ACh plus 10 μM GTP, 8-bromo-cGMP (100 μM) caused a rightward shift of the free Ca2+ concentration-response curve, significantly increasing the EC50for free Ca2+ from 0.35 ± 0.03 to 0.75 ± 0.06 μM; this effect of 8-bromo-cGMP was concentration dependent from 1 to 100 μM. 8-Bromo-cGMP (100 μM) decreased the level of regulatory myosin light chain (rMLC) phosphorylation for a given cytosolic Ca2+ concentration but had no effect on the amount of isometric force produced for a given level of rMLC phosphorylation. These findings suggest that cGMP decreases Ca2+ sensitivity in canine tracheal smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that modulate the relationship between cytosolic Ca2+ concentration and rMLC phosphorylation.

Effect of phorbol esters on Ca2+ sensitivity and myosin light-chain phosphorylation in airway smooth muscle

1998 ◽  
Vol 274 (5) ◽  
pp. C1253-C1260 ◽  
Author(s):  
Dorothee H. Bremerich ◽  
Tetsuya Kai ◽  
David O. Warner ◽  
Keith A. Jones
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Phorbol Esters ◽  
Isometric Force ◽  
Calphostin C ◽  
Regulatory Myosin Light Chain ◽  
Kinase C ◽  
The Relationship

We studied in β-escin-permeabilized canine tracheal smooth muscle (CTSM) the effect of the protein kinase C (PKC) agonist phorbol 12,13-dibutyrate (PDBu) on isometric force at a constant submaximal Ca2+ concentration (i.e., the effect on Ca2+ sensitivity) and regulatory myosin light-chain (rMLC) phosphorylation. PDBu increased Ca2+sensitivity, an increase associated with a concentration-dependent, sustained increase in rMLC phosphorylation. PDBu altered the relationship between rMLC phosphorylation and isometric force such that the increase in isometric force was less than that expected for the increase in rMLC phosphorylation observed. The effect of four PKC inhibitors [calphostin C, chelerythrine chloride, a pseudosubstrate inhibitor for PKC, PKC peptide-(19—31) (PSSI), and staurosporine] on PDBu-induced Ca2+ sensitization as well as the effect of calphostin C and PSSI on rMLC phosphorylation were determined. Whereas none of these compounds prevented or reversed the PDBu-induced increase in Ca2+sensitivity, the PDBu-induced increase in rMLC phosphorylation was inhibited. We conclude that PDBu increases rMLC phosphorylation by activation of PKC but that the associated PDBu-induced increases in Ca2+ sensitivity are mediated by mechanisms other than activation of PKC in permeabilized airway smooth muscle.

Myosin thick filament lability induced by mechanical strain in airway smooth muscle

2001 ◽  
Vol 90 (5) ◽  
pp. 1811-1816 ◽  
Author(s):  
Kuo-Hsing Kuo ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Lincoln E. Ford ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cross Sections ◽  
Structural Changes ◽  
Isometric Force ◽  
Mechanical Strain ◽  
Thick Filament ◽  
Functional Changes ◽  
Thick Filaments ◽  
Length Changes

Airway smooth muscle adapts to different lengths with functional changes that suggest plastic alterations in the filament lattice. To look for structural changes that might be associated with this plasticity, we studied the relationship between isometric force generation and myosin thick filament density in cell cross sections, measured by electron microscope, after length oscillations applied to the relaxed porcine trachealis muscle. Muscles were stimulated regularly for 12 s every 5 min. Between two stimulations, the muscles were submitted to repeated passive ±30% length changes. This caused tetanic force and thick-filament density to fall by 21 and 27%, respectively. However, in subsequent tetani, both force and filament density recovered to preoscillation levels. These findings indicate that thick filaments in airway smooth muscle are labile, depolymerization of the myosin filaments can be induced by mechanical strain, and repolymerization of the thick filaments underlies force recovery after the oscillation. This thick-filament lability would greatly facilitate plastic changes of lattice length and explain why airway smooth muscle is able to function over a large length range.

Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness

1986 ◽  
Vol 70 (6) ◽  
pp. 571-575 ◽  
Author(s):  
Christopher Murlas
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Physiological Salt Solution ◽  
Induced Responses ◽  
Field Stimulation ◽  
Electrical Field ◽  
Airway Mucosa

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C. 2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed. 3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh. 4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium. 5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.

Combined Effect of Isoproterenol and Mechanical Oscillation on the Contractile Response of Mice Airway Smooth Muscle From Healthy and Asthmatic Subjects

2012 ◽  
Author(s):  
M. J. Jo-Avila ◽  
A. M. Al-Jumaily ◽  
J. Lu ◽  
L. Sobrevia
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Healthy Subjects ◽  
Contractile Response ◽  
Relaxation Response ◽  
Driving Mechanism ◽  
Airway Lumen ◽  
Mechanical Oscillations ◽  
Normal Breathing ◽  
Asthma Attack

The main driving mechanism during an asthma attack is the hyperconstriction of airway smooth muscle (ASM), which reduces the airway lumen and makes normal breathing difficult. The contraction can be relieved by using bronchodilator drugs such as Isoproterenol (ISO). This paper hypothesizes that mechanical oscillations may improve drug therapy when combined with ISO or used alone in asthmatic subjects. Preliminary results indicate that combining ISO with breathing equivalent mechanical oscillations tends to increase the relaxation response, as compared to ISO alone in airways from healthy subjects, but not in the same manner in asthmatic airways. The effect of superposed oscillations of 1% and 1.5% amplitude in the range 5–20 Hz applied over breathing equivalent mechanical oscillations was also assessed in the study.

Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species

2002 ◽  
Vol 80 (9) ◽  
pp. 865-871 ◽  
Author(s):  
Anabelle M. Opazo Saez ◽  
R Robert Schellenberg ◽  
Mara S Ludwig ◽  
Richard A Meiss ◽  
Peter D Paré
Keyword(s):  
Mechanical Properties ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Published Data ◽  
Passive Tension ◽  
Active Force ◽  
Muscle Shortening ◽  
Human Airways ◽  
Tissue Elastance

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus ~60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only ~12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (~22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to ~9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.Key words: isometric force, isotonic shortening, elastance.

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