Independent pathways regulate the cytosolic [Ca2+] initial transient and subsequent oscillations in individual cultured arterial smooth muscle cells responding to extracellular ATP.

Mahoney, Mỹ G.; Randall, Catherine J.; Linderman, Jennifer J.; Gross, David J.; Slakey, Linda L.

doi:10.1091/mbc.3.5.493

Cited by 21 publications

(21 citation statements)

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“…However, the contractile responses of these cells were not investigated. By contrast, ATP-induced Ca 2ϩ signaling is better characterized in vascular SMCs (e.g., from the pulmonary artery), where it was found that ATP could induce a series of Ca 2ϩ oscillations (14,21,26). Consequently, the objective of the present study was to characterize the effect of ATP on the Ca 2ϩ signaling…”

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confidence: 93%

ATP stimulates Ca²⁺oscillations and contraction in airway smooth muscle cells of mouse lung slices

Bergner

Sanderson

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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2ϩ oscillations that were accompanied by airway contraction. After ϳ1 min, the Ca 2ϩ oscillations subsided and the airway relaxed. By contrast, Ն0.5 M adenosine 5Ј-O-(3-thiotriphosphate) (nonhydrolyzable) induced Ca 2ϩ oscillations in the SMCs and an associated airway contraction that persisted for Ͼ2 min. Adenosine 5Ј-O-(3-thiotriphosphate)-induced Ca 2ϩ oscillations occurred in the absence of external Ca 2ϩ but were abolished by the phospholipase C inhibitor U-73122 and the inositol 1,4,5-trisphosphate receptor inhibitor xestospongin. Adenosine, AMP, and ␣,␤-methylene ATP had no effect on airway caliber, and the magnitude of the contractile response induced by a variety of nucleotides could be ranked in the following order: ATP ϭ UTP Ͼ ADP. These results suggest that the SMC response to ATP is impaired by ATP hydrolysis and mediated via P2Y 2 or P2Y 4 receptors, activating phospholipase C to release Ca 2ϩ via the inositol 1,4,5-trisphosphate receptor. We conclude that ATP can serve as a spasmogen of airway SMCs and that Ca 2ϩ oscillations in SMCs are required to sustain airway contraction. calcium signaling; confocal microscopy; ATP hydrolysis ASTHMA IS AN AIRWAY DISEASE characterized by a hyperreactive response of airway smooth muscle cells (SMCs) to spasmogens such as histamine, leukotrienes, and perhaps serotonin (2, 6, 25). A major source of histamine and other agonists is an exocytotic release from inflammatory cells (i.e., mast cells and basophils) within the submucosal tissue, in close proximity to the SMCs. However, mast cell degranulation can simultaneously release another potential spasmogen, ATP, which is packaged in the same exocytotic vesicles (23). In addition, airway epithelial cells have also been identified as a source of extracellular ATP. Although the active release mechanisms of ATP from epithelial cells are not understood (5,7,11,36,37), epithelial trauma associated with asthma (12, 18) can result in damaged cells that passively release ATP.In many other tissues, ATP has been found to stimulate P2X and P2Y receptors, both of which have been identified in lung tissue (19,29,34,35 ] i ) of SMCs usually result in the phosphorylation of myosin light chain and the stimulation of contraction (15, 16), ATP is likely to be a potent spasmogen of airway SMCs.Surprisingly, the effects of ATP on the [Ca 2ϩ ] i of airway SMCs or on airway contraction have not been extensively studied, and the few reports that exist are inconsistent. For example, ATP was found to increase in vivo airway resistance in rats (9) or induce contraction in isolated guinea pig tracheae (8). On the other hand, ATP was reported to relax rabbit tracheal smooth muscle strips (1) and isolated mouse trachea (10, 17) that had been previously contracted with acetylcholine (ACh). These tissue preparations were derived from the large airways and consisted of tracheal rings or strips. As a result, these studies were not able to focus on the responses of individual SMCs. In addition, it is not clear whether results obtained from large air...

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confidence: 93%

ATP stimulates Ca²⁺oscillations and contraction in airway smooth muscle cells of mouse lung slices

Bergner

Sanderson

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The initial rise in [Ca 2+ ] c in response to InsP 3 -generating transmitters has been attributed, traditionally, to a large transient release from the SR (sarcoplasmic reticulum), followed by a secondary, lower sustained increase in [Ca 2+ ] c to above resting levels, the latter depending on extracellular Ca 2+ influx through sarcolemmal Ca 2+ channels [4]. However, re-examination of the changes in [Ca 2+ ] c in single cells within tissues has shown that each cell does not respond to stimulation with a co-ordinated transient and a sustained increase in [Ca 2+ ] c [5][6][7][8]. Rather, at the subcellular level, Ca 2+ signals appear as localized eventsCa 2+ 'puffs' and 'sparks' -which are restricted to a small area of the cell and which comprise the elementary components of the global Ca 2+ response [9,10].…”

Section: Introductionmentioning

confidence: 99%

Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle

McCarron

Bradley

MacMillan

et al. 2003

Biochemical Society Transactions

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Smooth muscle cells respond to InsP(3)-generating (sarcolemma-acting) neurotransmitters and hormones by releasing Ca(2+) from the internal store. However, the release of Ca(2+) does not occur uniformly throughout the cytoplasm but often into a localized area before being transmitted to other regions of the cell in the form of Ca(2+) waves and oscillations to actively spread information within and between cells. Yet, despite their significance, our understanding of the generation of oscillations to waves is incomplete. A major aspect of controversy centres on whether or not Ca(2+) released from the InsP(3) receptor activates RyRs (ryanodine receptors) to generate further release by Ca(2+)-induced Ca(2+) release and propagate waves or whether the entire process arises from InsP(3) receptor activity alone. Under normal physiological conditions the [Ca(2+)] required to activate RyR (approx. 15 microM) exceeds the bulk average [Ca(2+)](c) (cytoplasmic Ca(2+) concentration) generated by InsP(3) receptor activity (<1 microM). Progression of waves and oscillations by RyR activity would require a loss of control of RyR activity and an unrestrained positive feedback on Ca(2+) release. Under store-overload conditions, RyR Ca(2+) sensitivity is increased and this enables waves to be induced by RyR activity. However, the relevance of these Ca(2+)-release events to normal physiological functioning is unclear. The InsP(3) receptor, on the other hand, is activated by Ca(2+) over the physiological range (up to 300 nM) and deactivated by higher [Ca(2+)](c) (>300 nM), features that favour intermittent activity of the receptor as occurs in waves and oscillations. Experimental evidence for the involvement of RyR relies mainly on pharmacological approaches in the intact cell where poor drug specificity could have led to ambiguous results. In this brief review the possible interactions between InsP(3) receptors and RyR in the generation of oscillations and waves will be discussed. Evidence is presented that RyRs are not required for InsP(3)-mediated Ca(2+) transients. Notwithstanding, ryanodine can inhibit InsP(3)-mediated Ca(2+) responses after RyR activity has been induced by caffeine or by steady depolarization which evokes spontaneous transient outward currents (a sarcolemmal manifestation of RyR activity). Ryanodine inhibits InsP(3)-mediated Ca(2+) transients by depleting the store of Ca(2+) rather than by RyR involvement in the InsP(3)-mediated Ca(2+) increase.

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“…These single-cell [Ca2+li measurements have shown a broad degree of heterogeneity in the calcium response. Mahoney et al (5) have observed that the fraction of cells displaying a primary rise in [Ca2+]i following ligand stimulation is ligand concentration dependent. A lag time, or latency, in the onset of the rise in [Ca2+li following ligand stimulation has been observed in many cell types, including fibroblasts (6), HIT insulinoma cells (7), hepatocytes (8,9), and A10 cells (9).…”

Section: Introductionmentioning

confidence: 99%

Calcium Signaling in Individual BC³H1 Cells: Speed of Calcium Mobilization and Heterogeneity

Mahama

Linderman

1994

Biotechnology Progress

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Receptor/ligand binding on a cell surface may activate the calcium signal transduction cascade, resulting in the release of calcium from intracellular stores into the cytosol. Changes in intracellular free calcium, [Ca2+]i, following ligand stimulation have been linked to a variety of cell responses, from muscle contraction to hormone secretion. We have monitored changes in [Ca2+]i in single smooth muscle‐like BC3H1 cells following stimulation by the vasoconstrictor phenylephrine, using the fluorescent calcium probe, fura‐2, in a digital fluorescence imaging system. We find that not all cells respond to ligand stimulation with changes in [Ca2+]i. In addition, cells which respond to ligand stimulation exhibit considerable heterogeneity in the speed of calcium mobilization for a given ligand concentration. Both the population‐averaged speed for calcium mobilization and the fraction of cells which respond to ligand stimulation are increasing functions of the ligand concentration. In contrast, the magnitude of the ligand‐stimulated increase in [Ca2+]i from basal to peak levels in responding cells is independent of ligand concentration. We postulate that the heterogeneity seen in the ligand‐induced mobilization of calcium among single cells is a function of distinct differences between cells, such as number of receptors, size of the intracellular calcium store, or phospholipase C activity. We have developed a mathematical model, based on the calcium signal transduction cascade, to predict single‐cell calcium responses to ligand stimulation. We have systematically incorporated cell‐to‐cell parameter heterogeneity into the model by randomly selecting single‐cell parameter values from a Gaussian distribution. Model simulations predict both single‐cell and population‐averaged trends that we have observed experimentally. The results of this work suggest that increases in a population response may be the result of increased participation in the response as opposed to increases in the magnitudes of individual cell responses.

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Independent pathways regulate the cytosolic [Ca2+] initial transient and subsequent oscillations in individual cultured arterial smooth muscle cells responding to extracellular ATP.

Abstract: Stimulation with extracellular ATP causes a rapid initial transient rise followed by asynchronous periodic oscillations in cytosolic calcium ion activity ([Ca2+]

Cited by 21 publications

References 38 publications

ATP stimulates Ca²⁺oscillations and contraction in airway smooth muscle cells of mouse lung slices

ATP stimulates Ca²⁺oscillations and contraction in airway smooth muscle cells of mouse lung slices

Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle

Calcium Signaling in Individual BC³H1 Cells: Speed of Calcium Mobilization and Heterogeneity

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Independent pathways regulate the cytosolic [Ca2+] initial transient and subsequent oscillations in individual cultured arterial smooth muscle cells responding to extracellular ATP.

Abstract: Stimulation with extracellular ATP causes a rapid initial transient rise followed by asynchronous periodic oscillations in cytosolic calcium ion activity ([Ca2+]

Cited by 21 publications

References 38 publications

ATP stimulates Ca2+oscillations and contraction in airway smooth muscle cells of mouse lung slices

ATP stimulates Ca2+oscillations and contraction in airway smooth muscle cells of mouse lung slices

Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle

Calcium Signaling in Individual BC3H1 Cells: Speed of Calcium Mobilization and Heterogeneity

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ATP stimulates Ca²⁺oscillations and contraction in airway smooth muscle cells of mouse lung slices

ATP stimulates Ca²⁺oscillations and contraction in airway smooth muscle cells of mouse lung slices

Calcium Signaling in Individual BC³H1 Cells: Speed of Calcium Mobilization and Heterogeneity