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.

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.

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%).

Epithelium-dependent contraction of airway smooth muscle caused by eosinophil MBP

1990 ◽  
Vol 259 (4) ◽  
pp. L294-L303 ◽  
Author(s):  
S. R. White ◽  
S. Ohno ◽  
N. M. Munoz ◽  
G. J. Gleich ◽  
C. Abrahams ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Topical Application ◽  
Isometric Force ◽  
Force Generation ◽  
Active Tension ◽  
Smooth Muscle Contractility ◽  
Threshold Response ◽  
In Situ Preparation

We have identified two distinct functions of the epithelium of guinea pig airways that modulate airway smooth muscle contractility in the presence of the major basic protein (MBP) of human eosinophilic granules: 1) active force generation resulting less than 1 min after epithelial contact with MBP; and 2) sustained, augmented force generation that does not depend on cytotoxic interference with the synthesis of an epithelial-derived inhibitory factor. To evaluate these influences, an in situ preparation of guinea pig trachea was developed that permitted direct, on-line measurement of isometric force generation in the underlying muscle. Direct application of 10(-8) mol/cm2 MBP to the surface of the epithelium elicited force generation that did not require the presence of a contractile agonist. Force generation began less than 1 min after MBP application and reached maximum active tension (AT) of 0.97 +/- 0.38 g/cm at 30 min (P less than 0.05 vs. baseline). Denatured MBP did not elicit active tension. MBP also caused augmented contraction to intravenous acetylcholine (ACh); 30 min after topical application of MBP, AT generated by 3 x 10(-7) mol/kg iv ACh was 0.85 +/- 0.14 vs. 0.55 +/- 0.08 g/cm in control animals (P less than 0.05). Threshold response to ACh (-8.1 +/- 0.3 log mol/kg) also decreased significantly after MBP (-9.1 +/- 0.4 log mol/kg) vs. baseline (P less than 0.01). Removal of the epithelium (confirmed histologically) abolished both direct contraction and augmented force generation to ACh caused by topical application of MBP to the airway muscle. These data suggest actions of MBP that have not been demonstrated previously: 1) activation of epithelial function that causes direct contraction of airway smooth muscle; and 2) independence of the MBP-induced effects from active tone elicited by other agonists. We also demonstrate that augmented contraction that does not depend on MBP blockade of tonic inhibitory secretion from the epithelium.

Effect of acidosis on tension and [Ca2+]iin rat cerebral arteries: is there a role for membrane potential?

1998 ◽  
Vol 274 (2) ◽  
pp. H655-H662 ◽  
Author(s):  
Hong-Li Peng ◽  
Peter E. Jensen ◽  
Holger Nilsson ◽  
Christian Aalkjær
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Isometric Force ◽  
Cerebral Arteries ◽  
Bathing Solution ◽  
Hypercapnic Acidosis ◽  
Small Arteries ◽  
Intracellular Ca ◽  
Intracellular Microelectrodes

The cellular mechanism responsible for the reduction of tension in cerebral small arteries to acidosis is not known. In this study the role of smooth muscle intracellular Ca2+ concentration ([Ca2+]i) and membrane potential for the relaxation to acidosis was investigated in isolated rat cerebral small arteries. Isometric force was measured simultaneously with [Ca2+]i(fura 2) or with membrane potential (intracellular microelectrodes), and acidosis was induced by increasing[Formula: see text] or reducing[Formula: see text] of the bathing solution. Both hypercapnic and normocapnic acidosis were associated with a reduction of intracellular pH [measured with 2′,7′-bis-(carboxyethyl)-5 (and -6)-carboxyfluorescein], caused relaxation, and reduced [Ca2+]i. However, whereas hypercapnic acidosis caused hyperpolarization, normocapnic acidosis was associated with depolarization. It is concluded that a reduction of [Ca2+]iis in part responsible for the direct effect of the acidosis on the vascular smooth muscle both during normo- and hypercapnia. The mechanism responsible for the reduction of [Ca2+]idiffers between the hypercapnic and normocapnic acidosis, being partly explained by hyperpolarization during hypercapnic acidosis, whereas it is seen despite depolarization during normocapnic acidosis.

Respiratory epithelium-dependent inhibition of protein kinase C of airway smooth muscle cells

1991 ◽  
Vol 70 (5) ◽  
pp. 2137-2144 ◽  
Author(s):  
M. Souhrada ◽  
J. F. Souhrada
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Respiratory Epithelium ◽  
Resting Membrane Potential ◽  
Induced Response ◽  
Kinase C

We have examined the effect of phorbol myristate acetate (PMA) on airway smooth muscle (ASM) in the presence and absence of respiratory epithelium (RE) and analyzed the dependence of this response on extracellular sodium, Na+/H+ exchange, calcium, and cyclooxygenase products; we determined both the resting membrane potential and isometric force developed by ASM preparations. Removal of RE had no effect on the values of the resting membrane potential of ASM cells. In the presence of RE in the preparation, both electrical and contractile responses to PMA (10(-5) M) were significantly different compared with the response of ASM to PMA without RE. When the RE was present, stimulation of protein kinase C caused only a biphasic response in both membrane potential and isometric force. In either the presence or absence of RE, amiloride (10(-5) M) and a low-sodium solution inhibited both electrical and contractile changes of ASM cells caused by PMA. In the presence or absence of RE, verapamil (10(-5) M) attenuated (P less than 0.05) both electrical and contractile responses of ASM cells as induced by PMA. Verapamil, however, had no effect on the last phase of PMA-induced response. Pretreatment of preparations with indomethacin (10(-6) M) changed the PMA-induced response of ASM with RE to a response usually observed in ASM without RE. Finally, the incubation of tracheal preparations without RE with prostaglandin E2 (10(-8) M) altered the response of these preparations in such a way that their electrical and contractile response to PMA was essentially identical to the PMA response observed in preparations with an intact RE.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Human small airway smooth muscle responses in vitro; Actions and interactions of methacholine, histamine and leukotriene C4

1986 ◽  
Vol 125 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Johan De Jongste ◽  
Harry Mons ◽  
Roel Van Strik ◽  
Ivan Bonta ◽  
Karel Kerrebijn
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Small Airway ◽  
Leukotriene C4 ◽  
Muscle Responses

Muscarinic receptor reserve of airway smooth muscle and the response to isoproterenol

1990 ◽  
Vol 68 (3) ◽  
pp. 1017-1023
Author(s):  
J. M. Madison
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
Important Determinant ◽  
Effective Concentration ◽  
Tracheal Smooth Muscle ◽  
Receptor Reserve ◽  
Force Transducers

It has been hypothesized that the muscarinic receptor reserve for contraction of airway smooth muscle is an important determinant of the potency with which isoproterenol relaxes submaximal muscarinic contractions. The goals of this study were to inactivate, with phenoxybenzamine, a fraction of the muscarinic receptors present in canine tracheal smooth muscle, and then to determine whether this decrease in muscarinic receptor reserve altered the potency with which isoproterenol relaxed submaximal muscarinic contractions. Strips of smooth muscle were suspended from force transducers in vitro and preincubated with either vehicle (untreated) or phenoxybenzamine (10(-5) M) for 30 min. For muscarinic contractions induced by carbachol that were approximately 70-80% of maximum, the half-maximally effective concentration of isoproterenol was 2.4 +/- 0.8 x 10(-7) M for untreated strips but 5.8 +/- 1.3 x 10(-9) M for strips treated with phenoxybenzamine (n = 6, P less than 0.05). We concluded that treatment with phenoxybenzamine increased the sensitivity of a submaximal muscarinic contraction to isoproterenol. The results support the hypothesis that the muscarinic receptor reserve for contraction is an important determinant of the potency with which isoproterenol relaxes submaximal muscarinic contractions.

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