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Type III InsP3 receptor channel stays open in the presence of increased calcium

Author

Listed:
  • Robert E. Hagar

    (University of Connecticut Health Center)

  • Angela D. Burgstahler

    (Yale University)

  • Michael H. Nathanson

    (Yale University)

  • Barbara E. Ehrlich

    (Yale University)

Abstract

The inositol 1,4,5-trisphosphate receptor (InsP3R) is the main calcium(Ca2+) release channel in most tissues. Three isoforms have been identified1,2,3,4,5,6, but only types I and II InsP3R have been characterized7,8. Here we examine the functional properties of the type III InsP3R because this receptor is restricted to the trigger zone from which Ca2+ waves originate9,10,11 and it has distinctive InsP3-binding properties12,13. We find that type III InsP3R forms Ca2+ channels with single-channel currents that are similar to those of type I InsP3R; however, the open probability of type III InsP3R isoform increases monotonically with increased cytoplasmic Ca2+ concentration, whereas the type I isoform has a bell-shaped dependence on cytoplasmic Ca2+. The properties of type III InsP3R provide positive feedback as Ca2+ is released; the lack of negative feedback allows complete Ca2+ release from intracellular stores. Thus, activation of type III InsP3R in cells that express only this isoform results in a single transient, but global, increase in the concentration of cytosolic Ca2+. The bell-shaped Ca2+-dependence curve of type I InsP3R is ideal for supporting Ca2+ oscillations, whereas the properties of type III InsP3R are better suited to signal initiation.

Suggested Citation

  • Robert E. Hagar & Angela D. Burgstahler & Michael H. Nathanson & Barbara E. Ehrlich, 1998. "Type III InsP3 receptor channel stays open in the presence of increased calcium," Nature, Nature, vol. 396(6706), pages 81-84, November.
    • Handle: RePEc:nat:nature:v:396:y:1998:i:6706:d:10.1038_23954
    DOI: 10.1038/23954
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