Flash photolysis of caged inositol 1,4,5-trisphosphate activates plasma membrane calcium current in human T cells

Sustained elevation of intracellular Ca²⁺ by cell surface receptors is often dependent on influx of Ca²⁺ across the plasma membrane through routes not involving voltage-gated Ca²⁺ channels. We demonstrate that intracellular release of inositol 1,4,5-trisphosphate (InsP₃), either from stimulation of transfected human muscarinic receptors or from photolytic release of caged InsP₃, activates whole cell Ca²⁺ current in the Jurkat T cell line. Whole cell voltage clamp recordings indicate that the current is carried by a Ca²⁺-selective channel that resembles T-type voltage-gated Ca²⁺ channels in relative conductance of different cation species. Elevation of internal Ca²⁺ inactivates the channel, whereas internal perfusion with inositol 1,3,4,5-tetrakisphosphate (InsP₄) does not affect it. Photolytic release of caged 1-(α-glycerophosphoryl)-inositol 4,5- bisphosphate, an analog of InsP₃ which activates InsP₃ receptors but is not readily metabolized to InsP₄, also activates the current. We conclude that generation of InsP₃ is sufficient to activate Ca²⁺-selective channels in the plasma membrane of T cells. InsP₃ may have its effect indirectly through depletion of Ca²⁺ stores, or directly with a plasma membrane-associated InsP₃ receptor.