Protoplasma

, Volume 249, Supplement 1, pp 39–48 | Cite as

The role of cytoplasmic nanospaces in smooth muscle cell Ca2+ signalling

Review Article

Abstract

We address the importance of cytoplasmic nanospaces in Ca2 +  transport and signalling in smooth muscle cells and how quantitative modelling can shed significant light on the understanding of signalling mechanisms. Increasingly more convincing evidence supports the view that these nanospaces—nanometre-scale spaces between organellar membranes, hosting cell signalling machinery—are key to Ca2 +  signalling as much as Ca2 +  transporters and Ca2 +  storing organelles. Our research suggests that the origin of certain diseases is to be sought in the disruption of the proper functioning of cytoplasmic nanospaces. We begin with a historical perspective on the study of smooth muscle cell plasma membrane–sarcoplasmic reticulum nanospaces, including experimental evidence of their role in the generation of asynchronous Ca2 +  waves. We then summarize how stochastic modelling approaches have aided and guided our understanding of two basic functional steps leading to healthy smooth muscle cell contraction. We furthermore outline how more sophisticated and realistic quantitative stochastic modelling is now being employed not only to deepen our understanding but also to aid in the hypothesis generation for further experimental investigation.

Keywords

Cytoplasmic nanospaces Calcium signalling Vascular smooth muscle Sarcoplasmic reticulum Stochastic computational model Random walk 

References

  1. Andrews SS, Addy NJ, Brent R, Arkin AP (2010) Detailed simulations of cell biology with Smoldyn 2.1. PLoS Comput Biol 6(3):e1000,705. doi:10.1371/journal.pcbi.1000705 CrossRefGoogle Scholar
  2. Blaustein MP, Lederer WJ (1999) Sodium/calcium exchange: its physiological implications. Physiol Rev 79(3):763–854PubMedGoogle Scholar
  3. van Breemen C, Saida K (1989) Cellular mechanisms regulating [Ca2+]i smooth muscle. Annu Rev Physiol 51:315–329. doi:10.1146/annurev.ph.51.030189.001531 PubMedCrossRefGoogle Scholar
  4. van Breemen C (1977) Calcium requirement for activation of intact aortic smooth muscle. J Physiol 272(2):317–329PubMedGoogle Scholar
  5. Dai JM, Syyong H, Navarro-Dorado J, Redondo S, Alonso M, van Breemen C, Tejerina T (2010) A comparative study of alpha-adrenergic receptor mediated Ca(2+) signals and contraction in intact human and mouse vascular smooth muscle. Eur J Pharmacol 629(1-3):82–88. doi:10.1016/j.ejphar.2009.11.055 PubMedCrossRefGoogle Scholar
  6. Demaurex N, Distelhorst C (2003) Cell biology. Apoptosis—the calcium connection. Science 300(5616):65–67. doi:10.1126/science.1083628 PubMedCrossRefGoogle Scholar
  7. Devine CE, Somlyo AV, Somlyo AP (1972) Sarcoplasmic reticulum and excitation–contraction coupling in mammalian smooth muscles. J Cell Biol 52(3):690–718PubMedCrossRefGoogle Scholar
  8. Elmoselhi AB, Blennerhassett M, Samson SE, Grover AK (1995) Properties of the sarcoplasmic reticulum Ca(2+)-pump in coronary artery skinned smooth muscle. Mol Cell Biochem 151(2):149–155PubMedCrossRefGoogle Scholar
  9. Fameli N, van Breemen C, Kuo KH (2007) A quantitative model for linking Na+ /Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain [Ca2+] oscillations in vascular smooth muscle. Cell Calcium 42(6):565–575. doi:10.1016/j.ceca.2007.02.001 PubMedCrossRefGoogle Scholar
  10. Fameli N, Kuo KH, van Breemen C (2009) A model for the generation of localized transient [Na+] elevations in vascular smooth muscle. Biochem Biophys Res Commun 389(3):461–465. doi:10.1016/j.bbrc.2009.08.166 PubMedCrossRefGoogle Scholar
  11. Gabella G (1971) Caveolae intracellulares and sarcoplasmic reticulum in smooth muscle. J Cell Sci 8(3):601–609PubMedGoogle Scholar
  12. Holmes ME, Samson SE, Wilson JX, Dixon SJ, Grover AK (2000) Ascorbate transport in pig coronary artery smooth muscle: Na(+) removal and oxidative stress increase loss of accumulated cellular ascorbate. J Vasc Res 37(5):390–398PubMedCrossRefGoogle Scholar
  13. Iino M, Kasai H, Yamazawa T (1994) Visualization of neural control of intracellular Ca2+ concentration in single vascular smooth muscle cells in situ. EMBO J 13(21):5026–5031PubMedGoogle Scholar
  14. Inesi G, Sumbilla C, Kirtley ME (1990) Relationships of molecular structure and function in Ca2(+)-transport ATPase. Physiol Rev 70(3):749–760PubMedGoogle Scholar
  15. Läuger P (1991) Electrogenic ion pumps. Sinauer Associates, SunderlandGoogle Scholar
  16. Lee CH, Poburko D, Sahota P, Sandhu J, Ruehlmann DO, van Breemen C (2001) The mechanism of phenylephrine-mediated [ca(2+)](i) oscillations underlying tonic contraction in the rabbit inferior vena cava. J Physiol 534(Pt 3):641–650PubMedCrossRefGoogle Scholar
  17. Lee CH, Poburko D, Kuo KH, Seow CY, van Breemen C (2002) Ca(2+) oscillations, gradients, and homeostasis in vascular smooth muscle. Am J Physiol Heart Circ Physiol 282(5):H1571–H1583. doi:10.1152/ajpheart.01035.2001 Google Scholar
  18. Lee CH, Kuo KH, Dai J, Leo JM, Seow CY, van Breemen C (2005) Calyculin-a disrupts subplasmalemmal junction and recurring Ca2+ waves in vascular smooth muscle. Cell Calcium 37(1):9–16. doi:10.1016/j.ceca.2004.06.002 PubMedCrossRefGoogle Scholar
  19. Lemos VS, Poburko D, Liao CH, Cole WC, van Breemen C (2007) Na+ entry via TRPC6 causes Ca2+ entry via NCX reversal in ATP stimulated smooth muscle cells. Biochem Biophys Res Commun 352(1):130–134. doi:10.1016/j.bbrc.2006.10.160 PubMedCrossRefGoogle Scholar
  20. Moore ED, Etter EF, Philipson KD, Carrington WA, Fogarty KE, Lifshitz LM, Fay FS (1993) Coupling of the Na+ /Ca2+ exchanger, Na+ /K+ pump and sarcoplasmic reticulum in smooth muscle. Nature 365(6447):657–660. doi:10.1038/365657a0 PubMedCrossRefGoogle Scholar
  21. Nazer MA, van Breemen C (1998) Functional linkage of Na(+)-Ca2+ exchange and sarcoplasmic reticulum Ca2+ release mediates Ca2+ cycling in vascular smooth muscle. Cell Calcium 24(4):275–283PubMedCrossRefGoogle Scholar
  22. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136(5):876–890. doi:10.1016/j.cell.2009.02.014 PubMedCrossRefGoogle Scholar
  23. Poburko D, Liao CH, Lemos VS, Lin E, Maruyama Y, Cole WC, van Breemen C (2007) Transient receptor potential channel 6-mediated, localized cytosolic [Na+] transients drive Na+ /Ca2+ exchanger-mediated Ca2+ entry in purinergically stimulated aorta smooth muscle cells. Circ Res 101(10):1030–1038. doi:10.1161/CIRCRESAHA.107.155531 PubMedCrossRefGoogle Scholar
  24. Poburko D, Fameli N, Kuo KH, van Breemen C (2008) Ca2+ signaling in smooth muscle: TRPC6, NCX and LNats in nanodomains. Channels (Austin) 2(1):10–12CrossRefGoogle Scholar
  25. Poburko D, Liao CH, van Breemen C, Demaurex N (2009) Mitochondrial regulation of sarcoplasmic reticulum Ca2+ content in vascular smooth muscle cells. Circ Res 104(1):104–112. doi:10.1161/CIRCRESAHA.108.180612 PubMedCrossRefGoogle Scholar
  26. Rizzuto R, Duchen MR, Pozzan T (2004) Flirting in little space: the ER/mitochondria Ca2+ liaison. Sci STKE 2004(215):re1. doi:10.1126/stke.2152004re1 CrossRefGoogle Scholar
  27. Stiles J, Bartol T (2001) Computational neuroscience: realistic modeling for experimentalists. Chap Monte Carlo methods for simulating realistic synaptic microphysiology using MCell. CRC, Boca Raton, pp 87–127Google Scholar
  28. Stiles JR, Helden DV, Bartol TM, Salpeter EE, Salpeter MM (1996) Miniature endplate current rise times less than 100 microseconds from improved dual recordings can be modeled with passive acetylcholine diffusion from a synaptic vesicle. Proc Natl Acad Sci U S A 93(12):5747–5752PubMedCrossRefGoogle Scholar
  29. Wang IY, Bai Y, Sanderson MJ, Sneyd J (2010) A mathematical analysis of agonist- and KCL-induced Ca(2+) oscillations in mouse airway smooth muscle cells. Biophys J 98(7):1170–1181. doi:10.1016/j.bpj.2009.12.4273 PubMedCrossRefGoogle Scholar
  30. Wray S, Burdyga T (2010) Sarcoplasmic reticulum function in smooth muscle. Physiol Rev 90(1):113–178. doi:10.1152/physrev.00018.2008 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Anesthesiology, Pharmacology and TherapeuticsThe University of British ColumbiaVancouverCanada

Personalised recommendations