Inositol 1,3,4,5‐tetrakisphosphate and inositol 1,4,5‐trisphosphate act by different mechanisms when controlling C2+ in mouse lacrimal acinar cells

Abstract

In internally perfused single lacrimal acinar cells the competitive inositol 1,4,5-trisphosphate (Ins 1,4,5-P₃)-antagonist heparin inhibits the ACh-evoked K⁺ current response mediated by internal Ca²⁺ and also blocks both the Ins 1,4,5-P₃-evoked transient as well as the sustained K⁺ current increase evoked by combined stimulation with internal Ins 1,4,5-P₃ and inositol 1,3,4,5-tetrakisphosphate (Ins 1,3,4,5-P₄). When, during sustained stimulation with both Ins 1,4,5-P₃ and Ins 1,3,4,5-P₄, one of the inositol polyphosphates is removed, the K⁺ current declines; whereas removal of Ins 1,4,5-P₃ results in an immediate termination of the response, removal of Ins 1,3,4,5-P₄ only causes a very gradual and slow reduction in the current. Ins 1,3,4,5-P₄ is therefore not an acute controller of Ca²⁺ release from stores into the cytosol, but modulates the release of Ca²⁺ induced by Ins 1,4,5,P₃ by an unknown mechanism, perhaps by linking Ins 1,4,5 P₃-sensitive and insensitive Ca²⁺ stores.