title: In permeabilised endothelial cells IP3-induced Ca2+ release is dependent on the cytoplasmic concentration of monovalent cations.
abstract: OBJECTIVE
  IP3-induced Ca2+ release from the intracellular stores plays a role in the production of vasoactive substances in the endothelium. In many cells, Ca2+ release is accompanied by an inward movement of K+ whose function may be to dissipate the potential difference created by the loss of positive charge from the internal stores. The existence of such a mechanism in endothelial cells was investigated.
  
  
  METHODS
  Using saponin-permeabilised bovine aortic endothelial (BAE) cells, the effects of K+ on the IP3-induced 45Ca2+ release were investigated.
  
  
  RESULTS
  Replacement of K+ with NMG inhibited IP3 (3 microM)-induced 45Ca2+ release by 55%. The ability of other ions to allow IP3-induced 45Ca2+ release was found to be K+ = Na+ > Cs+ > Rb+ >> Co2+. The K+ channel blockers TEA, 4AP and 3,4-DAP were found to significantly inhibit IP3-induced 45Ca2+ release by 16%, 36% and 27%, respectively.
  
  
  CONCLUSIONS
  The data suggest that Ca2+ release from intracellular stores is partly dependent on a movement of K+ through K+ channels in the store membranes. In contrast, 9AA (400 microM) and substitution with Co2+ abolished the response. Therefore, K+ is important for IP3-induced 45Ca2+ release, but other ions are also likely to act as counter-ions. 9AA and Co2+ probably act on sites other than those involving ER monovalent cation channels. The possibility that a counter-ion system plays a role in the activation of endothelial cells is discussed.
authors.affiliation: Department of Physiological Sciences, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Wood
authors.forename: J I
authors.initials: JI
authors.lastname: Gillespie
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000585:Aminacrine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D002417:Cattle; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D002412:Cations; D026902:Potassium Channel Blockers; D003035:Cobalt; D019789:Tetraethylammonium; D008536:Meglumine; D000585:Aminacrine; D015544:Inositol 1,4,5-Trisphosphate; D015761:4-Aminopyridine; D000077770:Amifampridine; D011188:Potassium; D002118:Calcium