Ca<sup>2+</sup>oscillations, gradients, and homeostasis in vascular smooth muscle

Lee, Cheng‐Han; Poburko, Damon; Kuo, Kuo‐Hsing; Seow, Chun Y.; Breemen, Cornelis van

doi:10.1152/ajpheart.01035.2001

Cited by 110 publications

(120 citation statements)

References 73 publications

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“…However, the importance of this process in the cGMP-mediated relaxing mechanism appears to be determined by poorly understood aspects of the mechanisms involved in the generation of force. Processes such as the degree of filling of capacitive Ca 2ϩ stores and the interactive nature of this store with systems that control influx, such as Ca 2ϩ -regulated K ϩ channels and cytosolic levels of Ca 2ϩ (15,22), may determine the importance of this mechanism in the observed relaxation to NO. Because TEA did not further attenuate cGMP-mediated relaxation to SNAP in the presence of CPA under conditions where TEA alone inhibited relaxation (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies also show that NO can cause vascular relaxation through stimulation of sarcoplasmic/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA) activity, thereby increasing Ca 2ϩ uptake through the sarcoplasmic reticulum (5). The increase in sarcoplasmic reticulum filling with Ca 2ϩ potentially influences additional systems associated with relaxation, including localized Ca 2ϩ release involved in the activation of Ca 2ϩ -activated K ϩ channels and other processes, through which store-operated mechanisms inhibit extracellular Ca 2ϩ influx elicited by contractile agents (15). Although it has been proposed that cGMPdependent and cGMP-independent mechanisms activate the uptake of Ca 2ϩ by SERCA in response to NO (5), the relative importance of these mechanisms remains to be investigated.…”

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confidence: 99%

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Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries

Mingone

Gupte

Iesaki

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mingone, Christopher J., Sachin A. Gupte, Takafumi Iesaki, and Michael S. Wolin. Hypoxia enhances a cGMPindependent nitric oxide relaxing mechanism in pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 285: L296-L304, 2003. First published April 11, 2003 10.1152/ ajplung.00362.2002 donors generally relax vascular preparations through cGMP-mediated mechanisms. Relaxation of endothelium-denuded bovine pulmonary arteries (BPA) and coronary arteries to the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) is almost eliminated by inhibition of soluble guanylate cyclase activation with 10 M 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), whereas only a modest inhibition of relaxation is observed under hypoxia (PO 2 ϭ 8-10 Torr). This effect of hypoxia is independent of the contractile agent used and is also observed with NO gas. ODQ eliminated SNAP-induced increases in cGMP under hypoxia in BPA. cGMP-independent relaxation of BPA to SNAP was not attenuated by inhibition of K ϩ channels (10 mM tetraethylammonium), myosin light chain phosphatase (0.5 M microcystin-LR), or adenylate cyclase (4 M 2Ј,5Ј-dideoxyadenosine). SNAP relaxed BPA contracted with serotonin under Ca 2ϩ -free conditions in the presence of hypoxia and ODQ, and contraction to Ca 2ϩ readdition was also attenuated. The sarcoplasmic reticulum Ca 2ϩ -reuptake inhibitor cyclopiazonic acid (0.2 mM) attenuated SNAP-mediated relaxation of BPA in the presence of ODQ. Thus hypoxic conditions appear to promote a cGMP-independent relaxation of BPA to NO by enhancing sarcoplasmic reticulum Ca 2ϩ reuptake. calcium; guanylate cyclase; nitrovasodilator IT IS WELL ACCEPTED that nitric oxide (NO) derived from the endothelium or nitrovasodilator drugs promotes vascular relaxation through stimulation of soluble guanylate cyclase (sGC) and generation of the mediator of smooth muscle relaxation cGMP (2,12,14). However, cGMP-independent mechanisms of smooth muscle relaxation have recently been reported (3,5,21,26). Multiple mechanisms have been identified through which cGMP induces smooth muscle relaxation, where the dominant system mediating relaxation appears to vary between the vascular segments and the experimental conditions. In smooth muscle, relaxation through cGMP is generally associated with multiple processes regulated by activation of cGMPdependent protein kinase that decrease intracellular Ca 2ϩ , the sensitivity of contraction to Ca 2ϩ , and the phosphorylation of myosin light chains (MLC) (17). NO can promote vascular relaxation through hyperpolarization by opening Ca 2ϩ -activated K ϩ channels through cGMP-dependent (1) and cGMP-independent (3) mechanisms. Recent studies also show that NO can cause vascular relaxation through stimulation of sarcoplasmic/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA) activity, thereby increasing Ca 2ϩ uptake through the sarcoplasmic reticulum (5). The increase in sarcoplasmic reticulum filling with Ca 2ϩ potentially influences additional systems associated with relaxation, including localized Ca 2ϩ release involved in the...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries

Mingone

Gupte

Iesaki

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Propagating waves of elevated intracellular [Ca 2+ ] have been characterized in the immature Xenopus laevis oocyte (13), mature eggs from a variety of species (14; 15; 16; 17), Ca 2+ -overloaded cardiac myocytes (18), vascular smooth muscle (19), and many other cell types (20; 21; 22; 23). In many cases intracellular Ca 2+ waves are primarily due to Ca 2+ release from internal stores, that is, they can occur in the absence of influx of Ca 2+ across the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

A bidomain threshold model of propagating calcium waves

2007

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We present a bidomain fire-diffuse-fire model that facilitates mathematical analysis of propagating waves of elevated intracellular calcium (Ca 2+ ) in living cells. Modelling Ca 2+ release as a threshold process allows the explicit construction of travelling wave solutions to probe the dependence of Ca 2+ wave speed on physiologically important parameters such as the threshold for Ca 2+ release from the endoplasmic reticulum (ER) to the cytosol, the rate of Ca 2+ resequestration from the cytosol to the ER, and the total [Ca 2+ ] (cytosolic plus ER). Interestingly, linear stability analysis of the bidomain fire-diffuse-fire model predicts the onset of dynamic wave instabilities leading to the emergence of Ca 2+ waves that propagate in a back-and-forth manner. Numerical simulations are used to confirm the presence of these so-called 'tango waves' and the dependence of Ca 2+ wave speed on the total [Ca 2+ ].

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“…The oscillatory electrical activity is not dependent on neuronal input in vivo [4], and can be measured in cultured arterial smooth muscle cells [5]. This spontaneous vasomotion is thought to assist in maintaining perfusion pressure and inhibiting tissue ischemia [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, these cells provide an excellent model for studying the spontaneous Ca 2+ oscillations, because confluent cells electrically couple, and show evidence of spontaneous oscillations that are synchronized among cells [2,3,5,14]. This accounts for the ability of single-cell oscillations to produce small, repetitive, constrictive and dilatory vasomotion in vessels, which are in contrast to other oscillations in vessels that appear to be more random and do not propagate between cells [7]. Under certain conditions 90% of all confluent cells have demonstrated spontaneous, repetitive Ca 2+ spikes in the presence of 1.5 mM extracellular Ca 2+ [3].…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Ca2+ oscillations in subcellular compartments of vascular smooth muscle cells rely on different Ca2+ pools

et al. 2004

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Spontaneous Ca 2+ oscillations in vascular smooth muscle cells have been modeled using a single Ca 2+ pool. This report describes spontaneous Ca 2+ oscillations dependent on two separate Ca 2+ sources for the nuclear versus cytoplasmic compartments. Changes in free intracellular Ca 2+ were monitored with ratiometric Ca 2+-fluorophores using confocal microscopy. On average, spontaneous oscillations developed in 79% of rat aortic smooth muscle cells that were synchronous between the cytoplasm and nucleus. Reduction of extracellular Ca 2+ (< 1 µM) decreased the frequency and amplitude of the cytoplasmic oscillations with 48% of the oscillations asynchronous between the nuclear and cytoplasmic compartments. Similar results were obtained with the Ca 2+ channel blockers, nimodipine and diltiazem. Arg-vasopressin (AVP) induced a rapid release of intracellular Ca 2+ stores that was greater in the nuclear compartment (4.20 ± 0.23 ratio units, n = 56) than cytoplasm (2.54 ± 0.28) in cells that had spontaneously developed prior oscillations. Conversely, cells in the same conditions lacking oscillations had a greater AVP-induced Ca 2+ transient in the cytoplasm (4.99 ± 0.66, n = 17) than in the nucleus (2.67 ± 0.29). Pre-treatment with Ca 2+ channel blockers depressed the AVP responses in both compartments with the cytoplasmic Ca 2+ most diminished. Depletion of internal Ca 2+ stores prior to AVP exposure blunted the nuclear response, mimicking the response of cells that lacked prior oscillations. Spontaneous oscillating cells had a greater sarcoplasmic reticulum network than cells that did not oscillate. We propose that spontaneous nuclear oscillations rely on perinuclear sarcoplasmic reticulum stores, while the cytoplasmic oscillations rely on Ca 2+ influx.

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Ca²⁺oscillations, gradients, and homeostasis in vascular smooth muscle

Cited by 110 publications

References 73 publications

Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries

Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries

A bidomain threshold model of propagating calcium waves

Spontaneous Ca2+ oscillations in subcellular compartments of vascular smooth muscle cells rely on different Ca2+ pools

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Ca2+oscillations, gradients, and homeostasis in vascular smooth muscle

Cited by 110 publications

References 73 publications

Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries

Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries

A bidomain threshold model of propagating calcium waves

Spontaneous Ca2+ oscillations in subcellular compartments of vascular smooth muscle cells rely on different Ca2+ pools

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Ca²⁺oscillations, gradients, and homeostasis in vascular smooth muscle