Depletion of InsP3 stores activates a Ca2+ and K+ current by means of a phosphatase and a diffusible messenger

Nature. 1993 Aug 26;364(6440):814-8. doi: 10.1038/364814a0.

Abstract

In non-excitable cells, release of Ca2+ from the inositol 1,4,5-trisphosphate (InsP3)-sensitive store can activate Ca2+ entry. Very little is known about the signal mechanism relating store emptying to plasma membrane Ca2+ influx. It has been suggested that the signal may be either a diffusible messenger like an inositol phosphate, or the InsP3 receptor itself, which, by physically coupling to some component of Ca2+ entry in the plasma membrane, may link store release to Ca2+ entry. The nature of the Ca2+ entry pathway is also unclear. Only in mast cells has a very selective Ca2+ current been observed after store emptying. Activation of exogenous 5-hydroxytryptamine (5-HT) receptors expressed in Xenopus oocytes or direct injection of InsP3 evokes Ca2+ entry activated by InsP3 pool depletion. Here we investigate the nature of this influx pathway and find a current activated by pool depletion. This has an unusual selectivity in that it is more permeable to Ca2+ ions than to other divalent cations (Ba2+, Sr2+ or Mn2+). Moreover, a K+ permeability is also stimulated after pool depletion. The activation of this store depletion current involves both a phosphatase and an unidentified diffusible messenger. Both the Ca2+ entry pathway and the activating factors found here may be relevant to pool-depleted Ca2+ entry in a variety of non-excitable cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cations, Divalent / metabolism
  • Cloning, Molecular
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electrophysiology
  • Ethers, Cyclic / pharmacology
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Okadaic Acid
  • Oocytes
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors
  • Phosphoric Monoester Hydrolases / metabolism*
  • Potassium / metabolism*
  • Rats
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism*
  • Second Messenger Systems* / drug effects
  • Serotonin / pharmacology
  • Xenopus

Substances

  • Cations, Divalent
  • Ethers, Cyclic
  • Receptors, Serotonin
  • Okadaic Acid
  • Serotonin
  • Egtazic Acid
  • Inositol 1,4,5-Trisphosphate
  • Phosphoric Monoester Hydrolases
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Potassium
  • Calcium