Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes

Abstract

Hydrolysis of membrane-associated phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)-P₂) to water soluble inositol 1,4,5-trisphosphate (Ins(l,4,5)P₃) is a common response by many different kinds of cells to a wide variety of external stimuli (see refs 1 and 2 for review). Ins (1,4,5)P₃ is a putative second messenger which increases intracellular Ca²⁺ by mobilizing internal Ca²⁺ stores, a hypothesis which has been substantiated by studies with chemically permeabilized cells^3–13 and with isolated microsomal membrane fractions^11,12–16. But the possibility that Ins(1,4,5)P₃ could induce in intact cells an influx of external Ca²⁺ through transmembrane channels, originally hypothesized by Michell in 1975¹⁷, has never been directly tested. We report here single-channel recordings of an Ins(1,4,5)P₃-activated conductance in excised patches of T-lymphocyte plasma membrane. The Ins(1,4,5)P₃-activated transmembrane channel appears to be identical to the recently described mitogen-regulated, voltage-insensitive Ca²⁺ permeable channel involved in T-cell activation¹⁸. We suggest that Ins(1,4,5)P₃ acts as the second messenger mediating transmembrane Ca²⁺ influx through specific Ca²⁺-permeable channels in mitogen-stimulated T-cell activation.