scholarly journals Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

1997 ◽  
Vol 4 (1) ◽  
pp. 13-20
Author(s):  
Luke J Janssen
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Calcium Channels ◽  
Airway Smooth Muscle ◽  
Calcium Ion ◽  
Membrane Conductance ◽  
Chloride Ion ◽  
Potassium Ion Channels ◽  
Therapeutic Implications ◽  
Transient Activation

Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM). Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization) and pathophysiology (airway hyperresponsiveness) are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

scholarly journals Calcium Handling in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

1998 ◽  
Vol 5 (6) ◽  
pp. 491-498 ◽  
Author(s):  
Luke J Janssen
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Calcium Handling ◽  
Muscle Physiology ◽  
Therapeutic Implications ◽  
Cellular Processes ◽  
Voltage Dependent ◽  
Complicated Model ◽  
Voltage Dependent Calcium Channels ◽  
Internal Calcium

Calcium plays a central role in the activation of many cellular processes, including the most relevant end-point in airway smooth muscle physiology: contraction. For this reason, the cytosolic concentration of calcium is tightly controlled by an elaborate array of mechanisms. The latter include multiple entry pathways from the extracellular space, a pump on the membrane that extrudes calcium out of the cell, an internal pump that sequesters calcium into an intracellular pool and at least two types of release sites from which sequestered calcium can be released back into the cytosol; all of these mechanisms are tightly regulated by second messenger-signalling pathways. Understanding of the relationship between calcium handling and contraction ("excitation-contraction coupling") has progressed from a mechanism in which activation of voltage-dependent calcium channels plays a central role (as in skeletal muscle) to a mechanism in which a small localized signalling event triggers a massive release of internal calcium (as in cardiac muscle) to a more complicated model in which the internal calcium pool divides the cytosol into two physiologically distinct spaces where the cytosolic concentration of calcium is regulated independently (as in vascular smooth muscle). The changes that may occur in calcium-handling pathways in asthma and the opportunities for novel approaches to the treatment of asthma are also discussed.

Dihydropyridine-sensitive single calcium channels in airway smooth muscle cells

1990 ◽  
Vol 259 (6) ◽  
pp. L468-L480 ◽  
Author(s):  
J. F. Worley ◽  
M. I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Calcium Channels ◽  
Smooth Muscle Cells ◽  
Calcium Channel ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Membrane Depolarization ◽  
Airway Smooth Muscle Cells ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

We have identified and characterized single voltage-dependent calcium channels in both acutely dissociated rat bronchial and cultured human tracheobronchial smooth muscle cells using the patch-clamp technique. In both cell types, on-cell membrane patches displayed unitary currents selective for barium ions and exhibited one conductance level (21–26 pS), and the open state probability was increased by membrane depolarization. Unitary barium currents were enhanced by the calcium channel selective agonist, BAY R 5417, and inhibited by the dihydropyridine calcium channel antagonist, nisoldipine (apparent inhibition constant less than 100 nM). Moreover, the degree of nisoldipine inhibition of the rat bronchial smooth muscle channels was increased with membrane depolarization in a manner consistent with the drug interacting with highest affinity to the inactivated channel state. In addition, the sensitivity to BAY R 5417 augmentation and nisoldipine inhibition of depolarization-induced tonic force of intact rat bronchial ring segments was in close agreement to the single channel results. Thus these data suggest that activation of voltage-dependent calcium channels can influence airway contraction and that dihydropyridines may be effective modulators of depolarization-induced increases in bronchial tone. We conclude that both rat and human airway smooth muscle cells have high-conductance voltage-dependent calcium channels that interact in a predictable manner with dihydropyridines and are similar to voltage-dependent calcium channels observed in other smooth muscle cells.

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.

Chloride and depolarization by acetylcholine in canine airway smooth muscle

1993 ◽  
Vol 71 (3-4) ◽  
pp. 284-292 ◽  
Author(s):  
E. E. Daniel ◽  
J. Jury ◽  
J.-P. Bourreau ◽  
L. Jager
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Chloride Channels ◽  
Reversal Potential ◽  
Chloride Ion ◽  
Resting Potential ◽  
Mechanical Responses ◽  
Intracellular Ca ◽  
Excitatory Junction Potentials ◽  
Sucrose Gap

The role of chloride channels has been examined in canine tracheal smooth muscle by recording mechanical responses to field stimulation and to acetylcholine (ACh) and by sucrose gap recording of excitatory junction potentials and ACh-induced electrical changes. The results of substitution studies using isethionate for chloride provided evidence that a chloride conductance contributes to the resting potential. The extrapolated reversal potential for ACh-induced depolarization was positive to the resting potential. Isethionate substitution inhibited ACh-induced depolarization, consistent with a contribution from increased Cl− conductance to the depolarization induced by ACh. However, closure of K+ channels and opening of a nonspecific cation channel could also contribute to depolarization. Further study of the effects of isethionate substitution during prolonged tissue exposure to chloride-free medium showed that retention or the accumulation of Ca2+ in intracellular stores was impaired. We conclude that effects of chloride deprivation on responses to ACh may reflect an early increase in Cl− conductance, but longer term changes reflect the requirement for this anion to maintain internal Ca2+ stores.Key words: chloride ion, airway smooth muscle, ion channels, release of intracellular Ca2+.

scholarly journals Paracetamol inhibits Ca2+ permeant ion channels and Ca2+ sensitization resulting in relaxation of precontracted airway smooth muscle

2020 ◽  
Vol 142 (2) ◽  
pp. 60-68
Author(s):  
Yuan-Yuan Chen ◽  
Meng-Fei Yu ◽  
Xiao-Xue Zhao ◽  
Jinhua Shen ◽  
Yong-Bo Peng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Airway Smooth Muscle
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