In permeabilised endothelial cells IP3-induced Ca2+ release is dependent on the cytoplasmic concentration of monovalent cations.

Abstract

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. Using saponin-permeabilised bovine aortic endothelial (BAE) cells, the effects of K+ on the IP3-induced 45Ca2+ release were investigated. 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. 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.