Rearrangement of the close contact between the mitochondria and the sarcoplasmic reticulum in airway smooth muscle

Cell Calcium ◽  
2005 ◽  
Vol 37 (4) ◽  
pp. 333-340 ◽  
Author(s):  
Jiazhen Dai ◽  
Kuo-Hsing Kuo ◽  
Joyce M. Leo ◽  
Cornelis van Breemen ◽  
Cheng-Han Lee
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Close Contact

scholarly journals Superficial buffer barrier and preferentially directed release of Ca2+ in canine airway smooth muscle

1999 ◽  
Vol 276 (5) ◽  
pp. L744-L753 ◽  
Author(s):  
Luke J. Janssen ◽  
Pierre A. Betti ◽  
Stuart J. Netherton ◽  
Denise K. Walters
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Cyclopiazonic Acid ◽  
Membrane Currents ◽  
Global Changes ◽  
Fura 2 ◽  
Mechanical Responses ◽  
Filling State

We examined cytosolic concentration of Ca2+([Ca2+]i) in canine airway smooth muscle using fura 2 fluorimetry (global changes in [Ca2+]i), membrane currents (subsarcolemmal [Ca2+]i), and contractions (deep cytosolic [Ca2+]i). Acetylcholine (10−4 M) elicited fluorimetric, electrophysiological, and mechanical responses. Caffeine (5 mM), ryanodine (0.1–30 μM), and 4-chloro-3-ethylphenol (0.1–0.3 mM), all of which trigger Ca2+-induced Ca2+ release, evoked Ca2+ transients and membrane currents but not contractions. The sarcoplasmic reticulum (SR) Ca2+-pump inhibitor cyclopiazonic acid (CPA; 10 μM) evoked Ca2+transients and contractions but not membrane currents. Caffeine occluded the response to CPA, whereas CPA occluded the response to acetylcholine. Finally, KCl contractions were augmented by CPA, ryanodine, or saturation of the SR and reduced when SR filling state was decreased before exposure to KCl. We conclude that 1) the SR forms a superficial buffer barrier dividing the cytosol into functionally distinct compartments in which [Ca2+]iis regulated independently; 2) Ca2+-induced Ca2+ release is preferentially directed toward the sarcolemma; and 3) there is no evidence for multiple, pharmacologically distinct Ca2+ pools.

scholarly journals Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle

2009 ◽  
Vol 297 (1) ◽  
pp. L26-L34 ◽  
Author(s):  
Venkatachalem Sathish ◽  
Michael A. Thompson ◽  
Jeffrey P. Bailey ◽  
Christina M. Pabelick ◽  
Y. S. Prakash ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Inflammation ◽  
Airway Smooth Muscle ◽  
Proinflammatory Cytokines ◽  
Cell Types ◽  
Human Airway Smooth Muscle ◽  
Inhibitory Protein ◽  
Intracellular Ca ◽  
Additional Exposure

Airway inflammation leads to increased intracellular Ca2+ ([Ca2+]i) levels in airway smooth muscle (ASM) cells. Sarcoplasmic reticulum Ca2+ release and reuptake are key components of ASM [Ca2+]i regulation. Ca2+ reuptake occurs via sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types. In human ASM, we tested the hypothesis that inflammation increases PLB, thus inhibiting SERCA function, and leading to maintained [Ca2+]i levels. Surprisingly, we found that human ASM does not express PLB protein (although mRNA is detectable). Overnight exposure to the proinflammatory cytokines TNFα and IL-13 did not induce PLB expression, raising the issue of how SERCA is regulated. We then found that direct SERCA phosphorylation (via CaMKII) occurs in human ASM. In fura-2-loaded human ASM cells, we found that the CaMKII antagonist KN-93 significantly slowed the rate of fall of [Ca2+]i transients induced by ACh or bradykinin (in zero extracellular Ca2+), suggesting a role for CaMKII-mediated SERCA regulation. SERCA expression was decreased by cytokine exposure, and the rate of fall of [Ca2+]i transients was slowed in cells exposed to TNFα and IL-13. Cytokine effects on Ca2+ reuptake were unaffected by additional exposure to KN-93. These data indicate that in human ASM, SERCA is regulated by mechanisms such as CaMKII and that airway inflammation maintains [Ca2+]i levels by decreasing SERCA expression and slowing Ca2+ reuptake.

Sarcoplasmic Reticulum Ca2+ Depletion by Caffeine and Changes of [Ca2+]i During Refilling in Bovine Airway Smooth Muscle Cells

2000 ◽  
Vol 31 (6) ◽  
pp. 558-563 ◽  
Author(s):  
Blanca Bazán-Perkins ◽  
Edgar Sánchez-Guerrero ◽  
Verónica Carbajal ◽  
Carlos Barajas-López ◽  
Luis M. Montaño
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells

scholarly journals Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca2+ regulation in airway smooth muscle (ASM)

2015 ◽  
Vol 93 (2) ◽  
pp. 97-110 ◽  
Author(s):  
Philippe Delmotte ◽  
Gary C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Transient Increase ◽  
Mitofusin 2 ◽  
Atp Production ◽  
Unfolded Protein ◽  
Ros Formation ◽  
Reactive Oxidant ◽  
Transient Elevation

Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca2+ ([Ca2+]cyt) responses to agonist stimulation and Ca2+ sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca2+]cyt induced by agonists leads to a transient increase in mitochondrial Ca2+ ([Ca2+]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca2+]mito is blunted despite enhanced [Ca2+]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion–ER/SR coupling, decreased mitochondrial Ca2+ buffering, mitochondrial fragmentation, and increased cell proliferation.

Role of Intracellular Ca2+Stores in the Inhibitory Effect of Halothane on Airway Smooth Muscle Contraction 

1998 ◽  
Vol 89 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Michiaki Yamakage ◽  
Shinji Kohro ◽  
Takashi Matsuzaki ◽  
Hideaki Tsuchida ◽  
Akoyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Muscle Tension ◽  
Inhibitory Effect ◽  
Intracellular Concentration ◽  
Dependent Manner ◽  
Release Channel ◽  
Dose Dependent

Background Halothane directly inhibits contraction of airway smooth muscle, mainly by decreasing the intracellular concentration of free Ca2+ ([Ca2+]i). The role of intracellular Ca2+ stores, sarcoplasmic reticulum, is still unclear. We investigated the role of sarcoplasmic reticulum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+]i and intracellular concentration of inositol 1,4,5-triphosphate ([IP3]i), a second messenger for release of Ca2+ from sarcoplasmic reticulum. Methods [Ca2+]i was monitored by measuring the 500-nm light emission ratio (F340/F380) of a Ca2+ indicator fura-2 with isometric tension of canine tracheal smooth muscle strip. During Ca2+-free conditions, carbachol (10(-5) M) was introduced with pretreatment of halothane (0-3%). During Ca2+-free conditions, 20 mM caffeine, a Ca2+-induced Ca2+ release channel opener, was introduced with or without halothane. We measured [IP3]i during exposure to carbachol and halothane by radioimmunoassay technique. Results Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+]i by 77% and muscle tension by 83% in a dose-dependent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+]i and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pretreatment with halothane abolished these responses. Rapid increase in [IP3]i produced by carbachol was significantly inhibited by 32% by halothane in a dose-dependent manner. Conclusions Halothane, during Ca2+-free conditions, inhibits transient contraction of airway smooth muscle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+]i. Depletion of Ca2+ from sarcoplasmic reticulum via Ca2+-induced Ca2+ release channels also may contribute to the attenuation of the increase in [Ca2+]i by halothane.

Regulation of sarcoplasmic reticulum Ca2+ reuptake in porcine airway smooth muscle

2008 ◽  
Vol 294 (4) ◽  
pp. L787-L796 ◽  
Author(s):  
Venkatachalem Sathish ◽  
Figen Leblebici ◽  
Sertac N. Kip ◽  
Michael A. Thompson ◽  
Christina M. Pabelick ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Small Interfering Rna ◽  
Regulatory Protein ◽  
Plasmic Reticulum ◽  
Intracellular Ca ◽  
Subsequent Exposure ◽  
Interfering Rna ◽  
Serca Inhibition

Regulation of intracellular Ca2+ concentration ([Ca2+]i) in airway smooth muscle (ASM) during agonist stimulation involves sarcoplasmic reticulum (SR) Ca2+ release and reuptake. The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) is key to replenishment of SR Ca2+ stores. We examined regulation of SERCA in porcine ASM: our hypothesis was that the regulatory protein phospholamban (PLN) and the calmodulin (CaM)-CaM kinase (CaMKII) pathway (both of which are known to regulate SERCA in cardiac muscle) play a role. In porcine ASM microsomes, we examined the expression and extent of PLN phosphorylation after pharmacological inhibition of CaM (with W-7) vs. CaMKII (with KN-62/KN-93) and found that PLN is phosphorylated by CaMKII. In parallel experiments using enzymatically dissociated single ASM cells loaded with the Ca2+ indicator fluo 3 and imaged using fluorescence microscopy, we measured the effects of PLN small interfering RNA, W-7, and KN-62 on [Ca2+]i responses to ACh and direct SR stimulation. PLN small interfering RNA slowed the rate of fall of [Ca2+]i transients to 1 μM ACh, as did W-7 and KN-62. The two inhibitors additionally slowed reuptake in the absence of PLN. In other cells, preexposure to W-7 or KN-62 did not prevent initiation of ACh-induced [Ca2+]i oscillations (which were previously shown to result from repetitive SR Ca2+ release/reuptake). However, when ACh-induced [Ca2+]i oscillations reached steady state, subsequent exposure to W7 or KN-62 decreased oscillation frequency and amplitude and slowed the fall time of [Ca2+]i transients, suggesting SERCA inhibition. Exposure to W-7 completely abolished ongoing ACh-induced [Ca2+]i oscillations in some cells. Preexposure to W-7 or KN-62 did not affect caffeine-induced SR Ca2+ release, indicating that ryanodine receptor channels were not directly inhibited. These data indicate that, in porcine ASM, the CaM-CaMKII pathway regulates SR Ca2+ reuptake, potentially through altered PLN phosphorylation.

The reverse mode of the Na+/Ca2+ exchanger provides a source of Ca2+ for store refilling following agonist-induced Ca2+ mobilization

2007 ◽  
Vol 292 (2) ◽  
pp. L438-L447 ◽  
Author(s):  
Simon Hirota ◽  
Evi Pertens ◽  
Luke J. Janssen
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Extracellular Domain ◽  
Selective Inhibitor ◽  
Cation Channels ◽  
Reverse Mode ◽  
Intracellular Ca

Agonist-induced contraction of airway smooth muscle (ASM) can be triggered by an elevation in the intracellular Ca2+ concentration, primarily through the release of Ca2+ from the sarcoplasmic reticulum (SR). The refilling of the SR is integral for subsequent contractions. It has been suggested that Ca2+ entry via store-operated cation (SOC) and receptor-operated cation channels may facilitate refilling of the SR. Indeed, depletion of the SR activates substantial inward SOC currents in ASM that are composed of both Ca2+ and Na+. Accumulation of Na+ within the cell may regulate Ca2+ handling in ASM by forcing the Na+/Ca2+ exchanger (NCX) into the reverse mode, leading to the influx of Ca2+ from the extracellular domain. Since depletion of the SR activates substantial inward Na+ current, it is conceivable that the reverse mode of the NCX may contribute to the intracellular Ca2+ pool from which the SR is refilled. Indeed, successive contractions of bovine ASM, evoked by various agonists (ACh, histamine, 5-HT, caffeine) were significantly reduced upon removal of extracellular Na+; whereas contractions evoked by KCl were unchanged by Na+ depletion. Ouabain, a selective inhibitor of the Na+/K+ pump, had no effect on the reductions observed under normal and zero-Na+ conditions. KB-R7943, a selective inhibitor of the reverse mode of the NCX, significantly reduced successive contractions induced by all agonists without altering KCl responses. Furthermore, KB-R7943 abolished successive caffeine-induced Ca2+ transients in single ASM cells. Together, these data suggest a role for the reverse mode of the NCX in refilling the SR in ASM following Ca2+ mobilization.

Intracellular Cl− fluxes play a novel role in Ca2+ handling in airway smooth muscle

2006 ◽  
Vol 290 (6) ◽  
pp. L1146-L1153 ◽  
Author(s):  
Simon Hirota ◽  
Nancy Trimble ◽  
Evi Pertens ◽  
Luke J. Janssen
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Benzoic Acid ◽  
Airway Smooth Muscle ◽  
Channel Blocker ◽  
Negative Charge ◽  
Ryanodine Receptors ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca ◽  
Uptake And Release

Intracellular Ca2+ is actively sequestered into the sarcoplasmic reticulum (SR), whereas the release of Ca2+ from the SR can be triggered by activation of the inositol 1,4,5-trisphosphate and ryanodine receptors. Uptake and release of Ca2+ across the SR membrane are electrogenic processes; accumulation of positive or negative charge across the SR membrane could electrostatically hinder the movement of Ca2+ into or out of the SR, respectively. We hypothesized that the movement of intracellular Cl− (Cl[Formula: see text]) across the SR membrane neutralizes the accumulation of charge that accompanies uptake and release of Ca2+. Thus inhibition of SR Cl− fluxes will reduce Ca2+ sequestration and agonist-induced release. The Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB; 10−4 M), previously shown to inhibit SR Cl− channels, significantly reduced the magnitude of successive acetylcholine-induced contractions of airway smooth muscle (ASM), suggesting a “run down” of sequestered Ca2+ within the SR. Niflumic acid (10−4 M), a structurally different Cl− channel blocker, had no such effect. Furthermore, NPPB significantly reduced caffeine-induced contraction and increases in intracellular Ca2+ concentration ([Ca2+]i). Depletion of Cl[Formula: see text], accomplished by bathing ASM strips in Cl−-free buffer, significantly reduced the magnitude of successive acetylcholine-induced contractions. In addition, Cl− depletion significantly reduced caffeine-induced increases in [Ca2+]i. Together these data suggest a novel role for Cl[Formula: see text] fluxes in Ca2+ handling in smooth muscle. Because the release of sequestered Ca2+ is the predominate source of Ca2+ for contraction of ASM, targeting Cl[Formula: see text] fluxes may prove useful in the control of ASM hyperresponsiveness associated with asthma.

Role of sarcoplasmic reticulum Ca 2+ content in Ca 2+ entry of bovine airway smooth muscle cells

2003 ◽  
Vol 368 (4) ◽  
pp. 277-283 ◽  
Author(s):  
Blanca Baz�n-Perkins ◽  
Edgar Flores-Soto ◽  
Carlos Barajas-L�pez ◽  
Luis M. Monta�o
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells
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