Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle

Balemba, Onesmo B.; Bartoo, Aaron C.; Nelson, Mark T.; Mawe, Gary M.

doi:10.1152/ajpgi.00415.2007

Cited by 29 publications

(30 citation statements)

References 55 publications

(87 reference statements)

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“…Smooth muscle accounts for the largest mass of tissue in the stomach, and it is therefore conceivable that the intense NCLX expression in the stomach results from its ubiquitous expression in smooth muscle (7). The essential role of the mitochondrial Na + /Ca 2+ exchanger in refilling smooth muscle Ca 2+ stores and in facilitating the Ca 2+ sparks leading to muscle contraction is documented (31,32) and agrees well with the high expression of NCLX in this tissue. A role of mitochondrial Na + /Ca 2+ exchange in insulin secretion is of profound physiological interest particularly because of the link between mitochondrial Ca 2+ levels and the rate of ATP synthesis, but is controversial because of potential interference of CGP-37157 with the L-type Ca 2+ channel activity (16).…”

Section: Discussionsupporting

confidence: 66%

NCLX is an essential component of mitochondrial Na ⁺ /Ca ²⁺ exchange

Palty

Silverman

Hershfinkel

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

709

560

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Section: Discussionsupporting

confidence: 66%

NCLX is an essential component of mitochondrial Na ⁺ /Ca ²⁺ exchange

Palty

Silverman

Hershfinkel

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

709

560

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“…Mitochondrial Ca 2ϩ fluxes can also regulate IP 3 R and RyR channel activities and thus SR Ca 2ϩ release (6,11,12,14,15,34,36). Here, the effects appear to be cell type specific, with both inhibition and promotion of SR Ca 2ϩ release being reported (6,11,12,15 Recently, the molecular identities of MCU [MCU/mitochondrial Ca 2ϩ uptake 1 (MICU1)] and NCX (also called NCLX) (7,21,22,47) have been uncovered, and the development of molecular tools may help us to better understand the relation between MCU and NCX with other established Ca 2ϩ regulatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Here, the effects appear to be cell type specific, with both inhibition and promotion of SR Ca 2ϩ release being reported (6,11,12,15 Recently, the molecular identities of MCU [MCU/mitochondrial Ca 2ϩ uptake 1 (MICU1)] and NCX (also called NCLX) (7,21,22,47) have been uncovered, and the development of molecular tools may help us to better understand the relation between MCU and NCX with other established Ca 2ϩ regulatory mechanisms. In this regard, studies examining MICU1 and NCX have relied on the specificity of Ru360 and CGP-37157 (18).…”

Section: Discussionmentioning

confidence: 99%

Inflammation alters regional mitochondrial Ca²⁺ in human airway smooth muscle cells

Delmotte

Yang

Thompson

et al. 2012

American Journal of Physiology-Cell Physiology

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Regulation of cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in airway smooth muscle (ASM) is a key aspect of airway contractility and can be modulated by inflammation. Mitochondria have tremendous potential for buffering [Ca(2+)](cyt), helping prevent Ca(2+) overload, and modulating other intracellular events. Here, compartmentalization of mitochondria to different cellular regions may subserve different roles. In the present study, we examined the role of Ca(2+) buffering by mitochondria and mitochondrial Ca(2+) transport mechanisms in the regulation of [Ca(2+)](cyt) in enzymatically dissociated human ASM cells upon exposure to the proinflammatory cytokines TNF-α and IL-13. Cells were loaded simultaneously with fluo-3 AM and rhod-2 AM, and [Ca(2+)](cyt) and mitochondrial Ca(2+) concentration ([Ca(2+)](mito)) were measured, respectively, using real-time two-color fluorescence microscopy in both the perinuclear and distal, perimembranous regions of cells. Histamine induced a rapid increase in both [Ca(2+)](cyt) and [Ca(2+)](mito), with a significant delay in the mitochondrial response. Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger (1 μM CGP-37157) increased [Ca(2+)](mito) responses in perinuclear mitochondria but not distal mitochondria. Inhibition of the mitochondrial uniporter (1 μM Ru360) decreased [Ca(2+)](mito) responses in perinuclear and distal mitochondria. CGP-37157 and Ru360 significantly enhanced histamine-induced [Ca(2+)](cyt). TNF-α and IL-13 both increased [Ca(2+)](cyt), which was associated with decreased [Ca(2+)](mito) in the case of TNF-α but not IL-13. The effects of TNF-α on both [Ca(2+)](cyt) and [Ca(2+)](mito) were affected by CGP-37157 but not by Ru360. Overall, these data demonstrate that in human ASM cells, mitochondria buffer [Ca(2+)](cyt) after agonist stimulation and its enhancement by inflammation. The differential regulation of [Ca(2+)](mito) in different parts of ASM cells may serve to locally regulate Ca(2+) fluxes from intracellular sources versus the plasma membrane as well as respond to differential energy demands at these sites. We propose that such differential mitochondrial regulation, and its disruption, may play a role in airway hyperreactivity in diseases such as asthma, where [Ca(2+)](cyt) is increased.

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“…Later studies also included a much higher concentration of HEPES plus phophocreatine (in addition to ATP) [17,49,67] as well as oligomycin (to prevent ATP synthetase activity [17]) to ensure that neither pH changes nor ATP depletion accounted for the slowing of Ca 2+ removal when mitochondria were inhibited. Support for the proposal that mitochondria accumulate Ca 2+ following entry of the ion across the plasma membrane now comes from a wide variety of blockers, including the uniporter inhibitor Ru360, the complex I inhibitor rotenone, the Na + -Ca 2+ exchange inhibitor CGP-37157 or experimental conditions saturating mitochondria with Ca 2+ [4,17,18,67]. Ca 2+ release from the SR via RyR is also modulated by mitochondria in smooth muscle.…”

Section: Mitochondrial Regulation Of Smooth Muscle Ca 2+ Signalsmentioning

confidence: 99%

Mitochondrial regulation of cytosolic Ca2+ signals in smooth muscle

McCarron

Olson

Chalmers

2012

Pflugers Arch - Eur J Physiol

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The cytosolic Ca²⁺ concentration ([Ca²⁺]c) controls virtually every activity of smooth muscle, including contraction, migration, transcription, division and apoptosis. These processes may be activated by large (>10 μM) amplitude [Ca²⁺]c increases, which occur in small restricted regions of the cell or by smaller (<1 μM) amplitude changes throughout the bulk cytoplasm. Mitochondria contribute to the regulation of these signals by taking up Ca²⁺. However, mitochondria's reported low affinity for Ca²⁺ is thought to require the organelle to be positioned close to ion channels and within a microdomain of high [Ca²⁺]. In cultured smooth muscle, mitochondria are highly dynamic structures but in native smooth muscle mitochondria are immobile, apparently strategically positioned organelles that regulate the upstroke and amplitude of IP₃-evoked Ca²⁺ signals and IP₃ receptor (IP₃R) cluster activity. These observations suggest mitochondria are positioned within the high [Ca²⁺] microdomain arising from an IP₃R cluster to exert significant local control of channel activity. On the other hand, neither the upstroke nor amplitude of voltage-dependent Ca²⁺ entry is modulated by mitochondria; rather, it is the declining phase of the transient that is regulated by the organelle. Control of the declining phase of the transient requires a high mitochondrial affinity for Ca²⁺ to enable uptake to occur over the normal physiological Ca²⁺ range (<1 μM). Thus, in smooth muscle, mitochondria regulate Ca²⁺ signals exerting effects over a large range of [Ca²⁺] (∼200 nM to at least tens of micromolar) to provide a wide dynamic range in the control of Ca²⁺ signals.

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Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle

Abstract: Balemba OB, Bartoo AC, Nelson MT, Mawe GM. Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle.

Cited by 29 publications

References 55 publications

NCLX is an essential component of mitochondrial Na ⁺ /Ca ²⁺ exchange

NCLX is an essential component of mitochondrial Na ⁺ /Ca ²⁺ exchange

Inflammation alters regional mitochondrial Ca²⁺ in human airway smooth muscle cells

Mitochondrial regulation of cytosolic Ca2+ signals in smooth muscle

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Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle

Abstract: Balemba OB, Bartoo AC, Nelson MT, Mawe GM. Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle.

Cited by 29 publications

References 55 publications

NCLX is an essential component of mitochondrial Na + /Ca 2+ exchange

NCLX is an essential component of mitochondrial Na + /Ca 2+ exchange

Inflammation alters regional mitochondrial Ca2+ in human airway smooth muscle cells

Mitochondrial regulation of cytosolic Ca2+ signals in smooth muscle

Contact Info

Product

Resources

About

NCLX is an essential component of mitochondrial Na ⁺ /Ca ²⁺ exchange

NCLX is an essential component of mitochondrial Na ⁺ /Ca ²⁺ exchange

Inflammation alters regional mitochondrial Ca²⁺ in human airway smooth muscle cells