What drives calcium entry during [Ca2+]i oscillations?--challenging the capacitative model.
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.
Shuttleworth
T J
TJ
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, New York, USA. tshut@pharmacol.rochester.edu
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D013997:Time Factors
D007295:Inositol Phosphates; D002118:Calcium