The Control of Sub-plasma Membrane Calcium Signalling by the Plasma Membrane Calcium ATPase Pump PMCA4

  • Nicholas Stafford
  • Ludwig Neyses
  • Delvac OceandyEmail author
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol., volume 3)


Within cardiomyocytes cytosolic calcium levels rise and fall by an order of magnitude in each cardiac cycle, yet amidst the noise of this “global” calcium, a separate pool of “local” calcium is able to act as a second messenger in a multitude of signalling networks. The cell is equipped to deal with this through utilising the calcium-binding messenger protein calmodulin which in turn activates calcium/calmodulin-dependent targets and through compartmentalisation. This allows decoding of the calcium signal within such subcellular microdomains as the mitochondrion, the nucleus, the sarcoplasmic reticulum and the plasma membrane. In recent years our group and others have identified isoform 4 of the plasma membrane calcium/calmodulin-dependent ATPase (PMCA4) as a major regulator of local subplasmalemmal calcium in a number of cardiovascular cell types including the cardiomyocyte. Here we review techniques developed for the study of calcium levels local to PMCA4, the protein interaction and signalling complexes formed and regulated by the pump and the physiological implications of these in the heart and vascular systems.


Plasma membrane calcium ATPase Signal transduction Calcium microdomain Genetically encoded calcium indicator GCaMP2 


Compliance with Ethical Standards

Conflict of Interest Statement

The authors declare that they have no conflict of interest.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Nicholas Stafford
    • 1
  • Ludwig Neyses
    • 1
    • 2
  • Delvac Oceandy
    • 1
    Email author
  1. 1.Division of Cardiovascular SciencesThe University of ManchesterManchesterUK
  2. 2.University of LuxembourgEsch-sur-AlzetteLuxembourg

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