Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity

Sanderson, Michael J.; Delmotte, Philippe; Bai, Yan; Perez-Zogbhi, Jose F.

doi:10.1513/pats.200704-050vs

Cited by 106 publications

(113 citation statements)

References 86 publications

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“…The initial release occurs in the vicinity of the plasma membrane. It spreads into the cell through the regenerative release of Ca 2+ by the RyR and /or the IP3R in the form of an intracellular Ca 2+ wave travelling down the length of the cell [31][32][33]. When [Ca 2+ ]i is integrated over an entire cell with time, these Ca 2+ waves appear as rhythmical oscillations [34].…”

Section: Calcium Handling By the Sarco/endoplasmic Reticulum's Calciumentioning

confidence: 99%

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Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Lipskaia¹,

Limon²,

Bobe³

et al. 2012

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans

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Section: Calcium Handling By the Sarco/endoplasmic Reticulum's Calciumentioning

confidence: 99%

“…These Ca 2+ oscillations are maintained during receptor occupancy and are driven by an endogenous pacemaker mechanism, called the cellular Ca 2+ oscillator [12,33,34]. Ca 2+ oscillators were classified into two main types, the membrane oscillators and the cytosolic oscillators [48].…”

Section: Mechanisms Of Cytosolic Ca 2+ Oscillations In Vsmcmentioning

confidence: 99%

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Lipskaia¹,

Limon²,

Bobe³

et al. 2012

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans

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“…The IBC consists of two domains: a ␤-trefoil domain and an ␣-helical domain. Both the IP 3 -bound IBC and the SD have been crystallized separately (8,9), and more recently the crystal structures of the bound and apo forms of the LBD have been reported (10,11).…”

mentioning

confidence: 99%

Identification of Functionally Critical Residues in the Channel Domain of Inositol Trisphosphate Receptors

Bhanumathy

Fonseca

Morris

et al. 2012

Journal of Biological Chemistry

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Background: Mutagenesis was used to gain insights into the structure/function of IP 3 R channels. Results: Only 5 of 22 residues mutated proved essential for channel function. Conclusion: We propose that Ile-2588 and Ile-2589 are at the channel gate. Arg-2596, His-2630, and His-2635 maintain the structure of the pore and facilitate contacts critical for channel gating. Significance: A revised model of channel gating is proposed.

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“…Although airway SMCs contraction is determined by increases in intracellular calcium concentration ([Ca 2ϩ ] i ) linked with increases in Ca 2ϩ sensitivity (30), the relative contribution of the Ca 2ϩ signaling and Ca 2ϩ sensitivity to contraction appears to be specific to the type of the SMC (31). For example, mouse airway SMCs seem to have a low Ca 2ϩ sensitivity coupled with fast agonistinduced Ca 2ϩ oscillations, whereas mouse pulmonary arteriole SMCs appear to have higher Ca 2ϩ sensitivity coupled with slow agonist-induced Ca 2ϩ oscillations (1,25,26).…”

mentioning

confidence: 99%

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Bai

Sanderson²

2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bai Y, Sanderson MJ. The contribution of Ca 2ϩ signaling and Ca 2ϩ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice. Am J Physiol Lung Cell Mol Physiol 296: L947-L958, 2009. First published April 3, 2009 doi:10.1152/ajplung.90288.2008.-To determine the relative contributions of Ca 2ϩ signaling and Ca 2ϩ sensitivity to the contractility of airway smooth muscle cells (SMCs), we compared the contractile responses of mouse and rat airways with the lung slice technique. Airway contraction was measured by monitoring changes in airway lumen area with phase-contrast microscopy, whereas changes in intracellular calcium concentration ([Ca 2ϩ ]i) of the SMCs were recorded with laser scanning microscopy. In mice and rats, methacholine (MCh) or serotonin induced concentration-dependent airway contraction and Ca 2ϩ oscillations in the SMCs. However, rat airways demonstrated greater contraction compared with mice, in response to agonist-induced Ca 2ϩ oscillations of a similar frequency. Because this indicates that rat airway SMCs have a higher Ca 2ϩ sensitivity compared with mice, we examined Ca 2ϩ sensitivity with Ca 2ϩ -permeabilized airway SMCs in which the [Ca 2ϩ ]i was experimentally controlled. In the absence of agonists, high [Ca 2ϩ ]i induced a sustained contraction in rat airways but only a transient contraction in mouse airways. This sustained contraction of rat airways was relaxed by Y-23672, a Rho kinase inhibitor, but not affected by GF-109203X, a PKC inhibitor. The subsequent exposure of Ca 2ϩ -permeabilized airway SMCs, with high [Ca 2ϩ ]i, to MCh elicited a further contraction of rat airways and initiated a sustained contraction of mouse airways, without changing the [Ca 2ϩ ]i of the SMCs. Collectively, these results indicate that airway SMCs of rats have a substantially higher innate Ca 2ϩ sensitivity than mice and that this strongly influences the transduction of the frequency of Ca 2ϩ oscillations into the contractility of airway SMCs. lung slices; Ca 2ϩ oscillations; confocal microscopy; asthma; hyperresponsiveness ASTHMA IS CHARACTERIZED BY airway inflammation and airway hyperresponsiveness to nonspecific stimulation. Although airway inflammation is known to result in airway remodeling, airway hyperresponsiveness occurs in the early stages of asthma when no obvious airway remodeling is discernable. Consequently, the fundamental mechanism leading to the excessive contraction of airway smooth muscle cells (SMCs) remains unknown. A straightforward hypothesis is that the innate contractility of the SMCs has been enhanced in asthmatic airways. However, the experimental evidence addressing the contractile responses of asthmatic SMCs in vitro is inconsistent. Increased (4, 6, 18, 21), normal (4, 5, 10, 34), and even reduced (12, 33, 37) airway constriction has been reported in human asthmatic or animal airways. These discrepancies may also result from the different protocols, methods, and parameters used to evaluate SMCs contraction.To determine whether the cont...

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Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity

Cited by 106 publications

References 86 publications

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Identification of Functionally Critical Residues in the Channel Domain of Inositol Trisphosphate Receptors

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

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Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity

Cited by 106 publications

References 86 publications

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Identification of Functionally Critical Residues in the Channel Domain of Inositol Trisphosphate Receptors

The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

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The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice