Tissue Specificity: The Role of Organellar Membrane Nanojunctions in Smooth Muscle Ca2+ Signaling

  • Nicola FameliEmail author
  • A. Mark Evans
  • Cornelis van BreemenEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)


In this chapter we examine the importance of cytoplasmic nanojunctions—nanometer scale appositions between organellar membranes including the molecular transporters therein—to the cell signaling machinery, with specific reference to Ca2+ transport and signaling in vascular smooth muscle and endothelial cells. More specifically, we will consider the extent to which quantitative modeling may aid in the development of our understanding of these processes. Testament to the requirement for such approaches lies in the fact that recent studies have provided evermore convincing evidence in support of the view that cytoplasmic nanospaces may be as significant to the process of Ca2+ signaling as the Ca2+ transporters, release channels, and Ca2+-storing organelles themselves. Moreover, the disruption and/or dysfunction of cytoplasmic nanospaces may be central to the origin of certain diseases. By way of introduction, we provide a historical perspective on the identification of smooth muscle cell plasma membrane (PM)-sarcoplasmic reticulum (SR) nanospaces and the early evidence in support of their role in the generation of asynchronous Ca2+ waves. We then summarize how stochastic modeling approaches can aid and guide the development of our understanding of two basic functional steps leading to healthy smooth muscle cell contraction. We furthermore outline how more sophisticated and realistic quantitative stochastic modeling may be employed not only to test working hypotheses, but also to lead in their development in a manner that informs further experimental investigation. Finally, we consider more recently defined nanospaces such as the lysosome-SR junction, by way of demonstrating the importance of quantitative stochastic modeling to our understanding of signaling mechanisms.


Cytoplasmic nanojunctions ER junctions Calcium signaling Smooth muscle Endothelium Lysosomes Stochastic modeling 

Supplementary material

In this animation, we start from an extracellular view of one PM-SR nanospace. The PM is depicted in red. The light blue/green object is part of the SR. The dark blue hemispheres on it represent SERCA pumps and the yellow objects on the PM represent NCX. The white sphere within the nanospace is one Ca2+ undergoing three-dimensional random-walk motion. As the animation progresses, we are flying under the PM and inside the space between the PM and SR membrane and eventually out again. All the elements in this model are to scale, except for Ca2+, whose radius is ten times its Bohr radius for visibility (MPG 8720 kb)


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institute of BiophysicsMedical University of GrazGrazAustria
  2. 2.Department of Anesthesiology, Pharmacology and TherapeuticsThe University of British ColumbiaVancouverCanada
  3. 3.Centre for Integrative Physiology, College of Medicine and Veterinary MedicineUniversity of EdinburghEdinburghUK

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