Lateral inhibition of inositol 1,4,5-trisphosphate receptors by cytosolic Ca(2+)

Curr Biol. 1999 Oct 7;9(19):1115-8. doi: 10.1016/s0960-9822(99)80481-3.


Ryanodine and inositol 1,4,5-trisphosphate (IP(3)) receptors - two related families of Ca(2+) channels responsible for release of Ca(2+) from intracellular stores [1] - are biphasically regulated by cytosolic Ca(2+) [2] [3] [4]. It is thought that the resulting positive feedback allows localised Ca(2+)-release events to propagate regeneratively, and that the negative feedback limits the amplitude of individual events [5] [6]. Stimulation of IP(3) receptors by Ca(2+) occurs through a Ca(2+)-binding site that becomes exposed only after IP(3) has bound to its receptor [7] [8]. Here, we report that rapid inhibition of IP(3) receptors by Ca(2+) occurs only if the receptor has not bound IP(3). The IP(3) therefore switches its receptor from a state in which only an inhibitory Ca(2+)-binding site is accessible to one in which only a stimulatory site is available. This regulation ensures that Ca(2+) released by an active IP(3) receptor may rapidly inhibit its unliganded neighbours, but it cannot terminate the activity of a receptor with IP(3) bound. Such lateral inhibition, which is a universal feature of sensory systems where it improves contrast and dynamic range, may fulfil similar roles in intracellular Ca(2+) signalling by providing increased sensitivity to IP(3) and allowing rapid graded recruitment of IP(3) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channels / chemistry*
  • Calcium Channels / metabolism*
  • Calcium Signaling
  • Cells, Cultured
  • Cytosol / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors
  • Liver / metabolism
  • Rats
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Time Factors


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Calcium