Coupling mechanisms in airway smooth muscle

1990 ◽  
Vol 258 (4) ◽  
pp. L119-L133 ◽  
Author(s):  
R. F. Coburn ◽  
C. B. Baron
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Airway Smooth Muscle ◽  
Electromechanical Coupling ◽  
Cell Function ◽  
Surface Membrane ◽  
Smooth Muscles ◽  
Membrane Receptors ◽  
Airway Smooth Muscle Cells ◽  
Coupling Mechanisms

This review documents available information about coupling mechanisms involved in airway smooth muscle force development and maintenance and relaxation of force. Basic concepts, obtained from experiments performed on many different mammalian cell types, are in place regarding coupling between surface membrane receptors and cell function; these concepts are considered as a framework for understanding coupling between receptors and contractile proteins in smooth muscles and in airway smooth muscles. We have divided various components of coupling mechanisms into those dependent on changes in the surface membrane potential (electromechanical coupling) and those independent of the surface membrane potential (pharmacomechanical coupling). We have, to some degree, emphasized modulation of coupling mechanisms by intrasurface membrane microprocessing or by second messengers. A challenge for the future is to obtain a better understanding of how coupling mechanisms are altered or modulated during different phases of contractions evoked by a single agonist and under conditions of multiple agonist exposure to airway smooth muscle cells.

Sarcoplasmic reticulum and mitochondria as cation accumulation sites in smooth muscle

1973 ◽  
Vol 265 (867) ◽  
pp. 17-23 ◽  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Divalent Cation ◽  
Electromechanical Coupling ◽  
Surface Membrane ◽  
Smooth Muscles ◽  
Relative Volume ◽  
Electron Dense Material ◽  
Tubular System ◽  
Central Elements

A tubular system of sarcoplasmic reticulum that is not penetrated by extracellular markers is described in vertebrate smooth muscles. The sarcoplasmic reticulum forms fenestrations around the surface vesicles and also forms close appositions (an approximately 10 to 12 nm gap traversed by periodic electron dense material) with the non-specialized surface membrane. The morphological couplings are considered to be the most probable sites of electromechanical coupling of the action potential to the twitch contraction. The relative volume of the sarcoplasmic reticulum varies in functionally different (tonic and phasic) smooth muscles, and correlates with the ability of the different smooth muscles to contract in the absence of extracellular calcium. Electron opaque deposits of strontium are accumulated by peripheral and central elements of the sarcoplasmic reticulum. The accumulation of strontium and barium by mitochondria raises the possibility that, in addition to the sarcoplasmic reticulum, mitochondria may play a role in the regulation of intracellular divalent cation levels in vertebrate smooth muscle.

Localized mechanical stress induces time-dependent actin cytoskeletal remodeling and stiffening in cultured airway smooth muscle cells

2004 ◽  
Vol 287 (2) ◽  
pp. C440-C448 ◽  
Author(s):  
Linhong Deng ◽  
Nigel J. Fairbank ◽  
Ben Fabry ◽  
Paul G. Smith ◽  
Geoffrey N. Maksym
Keyword(s):  
Smooth Muscle ◽  
Mechanical Stress ◽  
Airway Smooth Muscle ◽  
Cell Function ◽  
Mechanical Strain ◽  
Cell Stiffness ◽  
Airway Smooth Muscle Cells ◽  
Airway Narrowing ◽  
Time Courses ◽  
Altered Cell

Mechanical stress (MS) causes cytoskeletal (CSK) and phenotypic changes in cells. Such changes in airway smooth muscle (ASM) cells might contribute to the pathophysiology of asthma. We have shown that periodic mechanical strain applied to cultured ASM cells alters the structure and expression of CSK proteins and increases cell stiffness and contractility (Smith PG, Moreno R, and Ikebe M. Am J Physiol Lung Cell Mol Physiol 272: L20–L27, 1997; and Smith PG, Deng L, Fredberg JJ, and Maksym GN. Am J Physiol Lung Cell Mol Physiol 285: L456–L463, 2003). However, the mechanically induced CSK changes, altered cell function, and their time courses are not well understood. Here we applied MS to the CSK by magnetically oscillating ferrimagnetic beads bound to the CSK. We quantified CSK remodeling by measuring actin accumulation at the sites of applied MS using fluorescence microscopy. We also measured CSK stiffness using optical magnetic twisting cytometry. We found that, during MS of up to 120 min, the percentage of beads associated with actin structures increased with time. At 60 min, 68.1 ± 1.6% of the beads were associated with actin structures compared with only 6.7 ± 2.8% before MS and 38.4 ± 5.5% in time-matched controls ( P < 0.05). Similarly, CSK stiffness increased more than twofold in response to the MS compared with time-matched controls. These changes were more pronounced than observed with contractile stimulation by 80 mM KCl or 10−4 M acetylcholine. Together, these findings imply that MS is a potent stimulus to enhance stiffness and contractility of ASM cells through CSK remodeling, which may have important implications in airway narrowing and dilation in asthma.

The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

2006 ◽  
Vol 291 (3) ◽  
pp. L312-L321 ◽  
Author(s):  
Abdelilah Soussi Gounni
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cell Function ◽  
Airway Smooth Muscle Cells ◽  
High Affinity ◽  
Cytokines And Chemokines ◽  
High Affinity Receptor ◽  
High Affinity Ige Receptor

The airway smooth muscle (ASM) has been typically described as a contractile tissue, responding to neurotransmitters and inflammatory mediators. However, it has recently been recognized that ASM cells can also secrete cytokines and chemokines and express cell adhesion molecules that are important for the perpetuation and modulation of airway inflammation. Recent progress has revealed the importance of IgE Fc receptors in stimulating and modulating the function of these cells. In particular, the high-affinity receptor for IgE (FcεRI) has been identified in primary human ASM cells in vitro and in vivo within bronchial biopsies of atopic asthmatic individuals. Moreover, activation of this receptor has been found to induce marked increases in the intracellular calcium concentrations and T helper 2 cytokines and chemokines release. This and other evidence discussed in this review provide an emerging view of FcεR/IgE network as a critical modulator of ASM cell function in allergic asthma.

scholarly journals Activation of endogenous GABAA channels on airway smooth muscle potentiates isoproterenol-mediated relaxation

2008 ◽  
Vol 295 (6) ◽  
pp. L1040-L1047 ◽  
Author(s):  
George Gallos ◽  
Neil R. Gleason ◽  
Yi Zhang ◽  
Sang-Woo Pak ◽  
J. R. Sonett ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Smooth Muscles ◽  
Airway Disease ◽  
Airway Smooth Muscle Cells ◽  
Neurokinin A ◽  
Therapeutic Implications ◽  
Reactive Airway Disease ◽  
Endogenous Gaba

Reactive airway disease predisposes patients to episodes of acute smooth muscle mediated bronchoconstriction. We have for the first time recently demonstrated the expression and function of endogenous ionotropic GABAA channels on airway smooth muscle cells. We questioned whether endogenous GABAA channels on airway smooth muscle could augment β-agonist-mediated relaxation. Guinea pig tracheal rings or human bronchial airway smooth muscles were equilibrated in organ baths with continuous digital tension recordings. After pretreatment with or without the selective GABAA antagonist gabazine (100 μM), airway muscle was contracted with acetylcholine or β-ala neurokinin A, followed by relaxation induced by cumulatively increasing concentrations of isoproterenol (1 nM to 1 μM) in the absence or presence of the selective GABAA agonist muscimol (10–100 μM). In separate experiments, guinea pig tracheal rings were pretreated with the large conductance KCa channel blocker iberiotoxin (100 nM) after an EC50 contraction with acetylcholine but before cumulatively increasing concentrations of isoproterenol (1 nM to 1 uM) in the absence or presence of muscimol (100 uM). GABAA activation potentiated the relaxant effects of isoproterenol after an acetylcholine or tachykinin-induced contraction in guinea pig tracheal rings or an acetylcholine-induced contraction in human endobronchial smooth muscle. This muscimol-induced potentiation of relaxation was abolished by gabazine pretreatment but persisted after blockade of the maxi KCa channel. Selective activation of endogenous GABAA receptors significantly augments β-agonist-mediated relaxation of guinea pig and human airway smooth muscle, which may have important therapeutic implications for patients in severe bronchospasm.

Contraction and depolarization induced by fetal bovine serum in airway smooth muscle

1994 ◽  
Vol 266 (5) ◽  
pp. L528-L535 ◽  
Author(s):  
N. A. Abdullah ◽  
M. Hirata ◽  
K. Matsumoto ◽  
H. Aizawa ◽  
R. Inoue ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Airway Smooth Muscle ◽  
Bovine Serum ◽  
Fetal Bovine Serum ◽  
Muscle Tone ◽  
Smooth Muscles ◽  
Resting Membrane Potential ◽  
Fetal Bovine ◽  
Sustained Increase

We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations < 0.1%, FBS induced a sustained increase in muscle tone. At concentrations < 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (< 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5-hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS.

Muscarinic excitation-contraction coupling mechanisms in tracheal and bronchial smooth muscles

2001 ◽  
Vol 91 (3) ◽  
pp. 1142-1151 ◽  
Author(s):  
Luke J. Janssen ◽  
Jennifer Wattie ◽  
Hwa Lu-Chao ◽  
Tracy Tazzeo
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Smooth Muscles ◽  
Rho Kinase ◽  
Cyclopiazonic Acid ◽  
Organ Bath ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Coupling Mechanisms ◽  
Sustained Responses

We investigated the mechanisms underlying muscarinic excitation-contraction coupling in canine airway smooth muscle using organ bath, fura 2 fluorimetric, and patch-clamp techniques. Cyclopiazonic acid (CPA) augmented the responses to submaximal muscarinic stimulation in both tracheal (TSM) and bronchial smooth muscles (BSM), consistent with disruption of the barrier function of the sarcoplasmic reticulum. During maximal stimulation, however, CPA evoked substantial relaxation in TSM but not BSM. CPA reversal of carbachol tone persisted in the presence of tetraethylammoium or high KCl, suggesting that hyperpolarization is not involved; CPA relaxations were absent in tissues preconstricted with KCl alone or by permeabilization with β-escin, ruling out a nonspecific effect on the contractile apparatus. Peak contractions were sensitive to inhibitors of tyrosine kinase (genistein) or Rho kinase (Y-27632). Sustained responses were dependent on Ca2+influx in TSM but not BSM; this influx was sensitive to Ni2+ but not La3+. In conclusion, there are several mechanisms underlying excitation-contraction coupling in airway smooth muscle, the relative importance of which varies depending on tissue and degree of stimulation.

Effect of IgG1 and its fragments on resting membrane potential of isolated tracheal myocytes

1993 ◽  
Vol 74 (4) ◽  
pp. 1948-1953 ◽  
Author(s):  
M. Souhrada ◽  
J. F. Souhrada
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Immune Serum ◽  
Resting Membrane Potential ◽  
Airway Smooth Muscle Cells ◽  
Type I ◽  
Trypan Blue Exclusion

We enzymatically isolated airway smooth muscle cells from the trachea of guinea pigs (400–600 g body wt). After removal of connective tissue, strips of trachealis muscle were cleaned under a dissecting microscope and incubated with collagenase (type I, 1 mg/ml) and elastase (type I, 15 U/ml) for 20 min. Cells were resuspended in Dulbecco's modified Eagle's medium and seeded on 1.5% gelatin-coated Petri dishes (35 mm). The viability of cells was assessed by trypan blue exclusion. Individual myocytes were impaled with glass microelectrodes (input resistance 90–100 M omega). Resting membrane potential (Em) was determined before and after administration of 1) immune serum, 2) highly purified specific immunoglobulin G1 (IgG1), and 3) enzymatically prepared fragments of IgG1-F(ab')2 and Fc. We found that 1) Em of isolated tracheal myocytes is -60.5 +/- 0.5 mV; 2) some myocytes exhibit spontaneous electrical rhythm with mean frequency of 16.9 +/- 12 min-1 and mean amplitude of 3.7 +/- 0.6 mV; 3) immune serum, IgG1, and Fc fragments induced a biphasic change in Em: the initial mean depolarization (-51.5 +/- 0.8 mV) was followed by a steady-state hyperpolarization (-68.3 +/- 0.6 mV); and 4) pretreatment of myocytes with amiloride (10(-5) M) or exposure of myocytes to a low-sodium environment prevented changes in Em induced by the passive in vitro sensitization. It is likely that airway smooth muscle cells have a low-affinity Fc receptor, the occupancy of which leads to activation of amiloride-sensitive sodium influx.

scholarly journals SARCOPLASMIC RETICULUM AND THE TEMPERATURE-DEPENDENT CONTRACTION OF SMOOTH MUSCLE IN CALCIUM-FREE SOLUTIONS

1971 ◽  
Vol 51 (3) ◽  
pp. 722-741 ◽  
Author(s):  
Andrew P. Somlyo ◽  
Carrick E. Devine ◽  
Avril V. Somlyo ◽  
Stanley R. North
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Extracellular Space ◽  
Room Temperature ◽  
Electromechanical Coupling ◽  
Contractile Response ◽  
Surface Membrane ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Free Cell

The contractile response of turtle oviduct smooth muscle to acetylcholine after 30 min of incubation of muscles in Ca-free, 4 mM ethylene (bis) oxyethylenenitrilotetraacetic acid (EGTA) solutions at room temperature was greater than the contractile response after 30 min of incubation in the Ca-free medium at 37°C. Incubation in Ca-free solution at 37°C before stimulation with acetylcholine in Ca-free solutions at room temperature also reduced the contractile response, suggesting that activator calcium was lost from the fibers at a faster rate at higher temperatures. Electron micrographs of turtle oviduct smooth muscle revealed a sarcoplasmic reticulum (SR) occupying approximately 4% of the nucleus- and mitochondria-free cell volume. Incubation of oviduct smooth muscle with ferritin confirmed that the predominantly longitudinally oriented structures described as the SR did not communicate with the extracellular space. The SR formed fenestrations about the surface vesicles, and formed close contacts (couplings) with the surface membrane and surface vesicles in oviduct and vena caval smooth muscle; it is suggested that these are sites of electromechanical coupling. Calculation of the calcium requirements for smooth muscle contraction suggest that the amount of SR observed in the oviduct smooth muscle could supply the activator calcium for the contractions observed in Ca-free solutions. Incubation of oviduct smooth muscle in hypertonic solutions increased the electron opacity of the fibers. A new feature of some of the surface vesicles observed in oviduct, vena caval, and aortic smooth muscle was the presence of approximately 10 nm striations running approximately parallel to the openings of the vesicles to the extracellular space. Thick, thin, and intermediate filaments were observed in turtle oviduct smooth muscle, although the number of thick filaments seen in the present study appeared less than that previously found in mammalian smooth muscles.

Electromechanical coupling of ferret airway smooth muscle in response to leukotriene C4

1989 ◽  
Vol 66 (6) ◽  
pp. 2533-2538 ◽  
Author(s):  
C. G. Murlas ◽  
C. A. Doupnik
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Airway Smooth Muscle ◽  
Electromechanical Coupling ◽  
Isometric Force ◽  
Force Generation ◽  
Base Line ◽  
Leukotriene C4 ◽  
Force Transducers ◽  
Intracellular Microelectrodes

We investigated the possible electrophysiological basis for the slow, prolonged force generation by airway smooth muscle (ASM) produced by leukotriene C4 (LTC4). Preparations of ASM were made from ferret trachea and placed in tissue microchambers for study. Some of these preparations were arranged so that force transducers and intracellular microelectrodes (with tip resistances of 30–80 M omega) could be used to measure isometric force and cell membrane potential (Em) simultaneously from ASM cells stimulated by LTC4. We found that ferret tracheal muscle was relatively sensitive to LTC4 and that this sensitivity was not significantly affected by atropine (1 microM), phentolamine (1 microM), propranolol (3 microM), and pyrilamine (1 microM). In a 1 nM solution of LTC4, Em was -54.0 +/- 1.2 mV from 18 impalements (n) from 6 animals (N) compared with a base-line value of -61.6 +/- 0.8 mV (n/N = 29/8, P less than 0.0005). This change did not lead to force generation, however. Higher concentrations of LTC4 led to progressive decreases in Em to which force generation was closely coupled. Concentrations greater than or equal to 70 nM led to phasic oscillations in Em of 0.6–0.8 Hz and 1.7 mV in amplitude, which were abolished by 10 microM verapamil, although the base-line Em was unaffected by this concentration. Although 300 nM LTE4 by itself caused only a small depolarization of ferret trachealis, it substantially antagonized the electromechanical responsiveness of this smooth muscle to LTC4. We conclude that ferret ASM is relatively sensitive to LTC4 and that there is an electrical basis for the slow, prolonged force generation caused by this mediator.

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