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Inositol 1,4,5-trisphosphate [InsP3(1,4,5)] is a major second messenger regulating Ca2+ signaling in excitable and nonexcitable cells. InsP3(1,4,5) is extensively metabolized through a network of phosphorylation and dephosphorylation steps to products with potential second messenger function. Inositol 1,3,4,5-tetrakisphosphate [InsP4(1,3,4,5)], the direct metabolite of InsP3(1,4,5), has also been associated with Ca2+ signaling, but whether InsP4(1,3,4,5) acts in combination with InsP3(1,4,5) or whether it regulates Ca2+ signaling directly and independently is unclear, particularly in neurons. We report that olfactory receptor neurons in the lobster (Panulirus argus) express an InsP4(1,3,4,5) receptor in the plasma membrane that is a functional channel. The channel differs in conductance, kinetics, and voltage sensitivity from two plasma membrane InsP3(1,4,5)-gated channels previously reported in these neurons. In close spatial proximity, the InsP4(1,3,4,5)-and InsP3(1,4,5)-gated channels interact reciprocally to alter the channels' open probabilities in what may be a novel mechanism for regulating Ca2+ entry in neurons.

Inositol 1,3,4,5-tetrakisphosphate-gated channels interact with inositol 1,4,5-trisphosphate-gated channels in olfactory receptor neurons.