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Review Open Access

Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review)

  • Authors:
    • Jorge Reyes‑García
    • Edgar Flores‑Soto
    • Abril Carbajal‑García
    • Bettina Sommer
    • Luis M. Montaño
  • View Affiliations / Copyright

    Affiliations: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, México, Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México 14080, México
    Copyright: © Reyes‑García et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2998-3008
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    Published online on: October 2, 2018
       https://doi.org/10.3892/ijmm.2018.3910
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Abstract

In airway smooth muscle, the intracellular basal Ca2+ concentration [b(Ca2+)i] must be tightly regulated by several mechanisms in order to maintain a proper airway patency. The b[Ca2+]i is efficiently regulated by sarcoplasmic reticulum Ca2+‑ATPase 2b, plasma membrane Ca2+‑ATPase 1 or 4 and by the Na+/Ca2+ exchanger. Membranal Ca2+ channels, including the L‑type voltage dependent Ca2+ channel (L‑VDCC), T‑type voltage dependent Ca2+ channel (T‑VDCC) and transient receptor potential canonical 3 (TRPC3), appear to be constitutively active under basal conditions via the action of different signaling pathways, and are responsible for Ca2+ influx to maintain b[Ca2+]i. The two types of voltage‑dependent Ca2+ channels (L‑ and T‑type) are modulated by phosphorylation processes mediated by mitogen‑activated protein kinase kinase (MEK) and extracellular‑signal‑regulated kinase 1 and 2 (ERK1/2). The MEK/ERK signaling pathway can be activated by G‑protein‑coupled receptors through the αq subunit when the endogenous ligand (i.e., acetylcholine, histamine, leukotrienes, etc.) is present under basal conditions. It may also be stimulated when receptor tyrosine kinases are occupied by the appropriate ligand (cytokines, growth factors, etc.). ERK1/2 phosphorylates L‑VDCC on Ser496 of the β2 subunit and Ser1928 of the α1 subunit, decreasing or increasing the channel activity, respectively, and enabling it to switch between an open and closed state. T‑VDCC is also probably phosphorylated by ERK1/2, although further research is required to identify the phosphorylation sites. TRPC3 is directly activated by diacylglycerol produced by phospholipase C (PLCβ or γ). Constitutive inositol 1,4,5‑trisphosphate production induces the release of Ca2+ from the sarcoplasmic reticulum through inositol triphosphate receptor 1. This ion induces Ca2+‑induced Ca2+ release through the ryanodine receptor 2 (designated as Ca2+ ‘sparks’). Therefore, several Ca2+ handling mechanisms are finely tuned to regulate basal intracellular Ca2+ concentrations. It is conceivable that alterations in any of these processes may render airway smooth muscle susceptible to develop hyperresponsiveness that is observed in ailments such as asthma.
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Copy and paste a formatted citation
Spandidos Publications style
Reyes‑García J, Flores‑Soto E, Carbajal‑García A, Sommer B and Montaño LM: Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review). Int J Mol Med 42: 2998-3008, 2018.
APA
Reyes‑García, J., Flores‑Soto, E., Carbajal‑García, A., Sommer, B., & Montaño, L.M. (2018). Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review). International Journal of Molecular Medicine, 42, 2998-3008. https://doi.org/10.3892/ijmm.2018.3910
MLA
Reyes‑García, J., Flores‑Soto, E., Carbajal‑García, A., Sommer, B., Montaño, L. M."Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review)". International Journal of Molecular Medicine 42.6 (2018): 2998-3008.
Chicago
Reyes‑García, J., Flores‑Soto, E., Carbajal‑García, A., Sommer, B., Montaño, L. M."Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review)". International Journal of Molecular Medicine 42, no. 6 (2018): 2998-3008. https://doi.org/10.3892/ijmm.2018.3910
Copy and paste a formatted citation
x
Spandidos Publications style
Reyes‑García J, Flores‑Soto E, Carbajal‑García A, Sommer B and Montaño LM: Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review). Int J Mol Med 42: 2998-3008, 2018.
APA
Reyes‑García, J., Flores‑Soto, E., Carbajal‑García, A., Sommer, B., & Montaño, L.M. (2018). Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review). International Journal of Molecular Medicine, 42, 2998-3008. https://doi.org/10.3892/ijmm.2018.3910
MLA
Reyes‑García, J., Flores‑Soto, E., Carbajal‑García, A., Sommer, B., Montaño, L. M."Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review)". International Journal of Molecular Medicine 42.6 (2018): 2998-3008.
Chicago
Reyes‑García, J., Flores‑Soto, E., Carbajal‑García, A., Sommer, B., Montaño, L. M."Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review)". International Journal of Molecular Medicine 42, no. 6 (2018): 2998-3008. https://doi.org/10.3892/ijmm.2018.3910
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