Mitochondrial regulation of cytosolic Ca2+ signals in smooth muscle

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages51-62
Number of pages11
JournalPflügers Archiv European Journal of Physiology
Volume464
Issue numberspecial issue
DOIs
Publication statusPublished - 2012

Fingerprint

Mitochondria
Muscle Mitochondrion
Smooth Muscle
Muscle
Organelles
Inositol 1,4,5-Trisphosphate Receptors
Muscle Contraction
Ion Channels
Cytoplasm
Apoptosis
Transcription
Electric potential

Keywords

  • mitochondrial regulation
  • cytosolic Ca2+
  • smooth muscle

Cite this

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title = "Mitochondrial regulation of cytosolic Ca2+ signals in smooth muscle",
abstract = "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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Mitochondrial regulation of cytosolic Ca2+ signals in smooth muscle. / McCarron, John; Olson, Marnie; Chalmers, Susan.

In: Pflügers Archiv European Journal of Physiology , Vol. 464, No. special issue, 2012, p. 51-62.

Research output: Contribution to journalArticle

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AU - Chalmers, Susan

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AB - 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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