What drives calcium entry during [Ca2+]i oscillations?--challenging the capacitative model

Cell Calcium. 1999 Mar;25(3):237-46. doi: 10.1054/ceca.1999.0022.


An increased entry of Ca2+ across the plasma membrane plays a key role in the generation and maintenance of the [Ca2+]i signals seen in cells following activation of receptors coupled to the PLC/InsP3 signaling pathway. In recent years, considerable efforts have been made to define the nature and control of this agonist-enhanced Ca2+ entry. To date, these studies have largely focussed on the so-called 'capacitative' or store-operated model and, although many important details remain unclear, the critical role this mechanism plays in maintaining the sustained elevated 'plateau' type of [Ca2+]i response seen at high agonist concentrations is now well established. Far less well understood is the nature of the enhanced Ca2+ entry associated with the more complex [Ca2+]i signals typical of stimulation at more physiological levels of agonist. Where such entry has been considered, it too has generally been assumed to result from a capacitative or 'store-operated' mechanism. Significantly, however, direct evidence in support of this assumption is lacking. This review attempts to critically examine this assumption and presents the argument that several key characteristics of capacitative or store-operated mechanisms of agonist-activated Ca2+ entry are incompatible with its operation during these types of [Ca2+]i signal.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Dose-Response Relationship, Drug
  • Inositol Phosphates / metabolism
  • Kinetics
  • Models, Biological
  • Time Factors


  • Inositol Phosphates
  • Calcium