A metabolically stable analog of 1,4,5-inositol trisphosphate activates a novel K⁺ conductance in pyramidal cells of the rat hippocampal slice

IP(s)₃, a metabolically stable analog of 1,4,5-inositol trisphosphate ON, inhibited action potential firing when injected into hippocampal pyramidal cells. This effect was associated with decreased input resistance, a more negative resting potential, outward rectification at depolarized potentials, and an afterhyperpolarization. The response to IP(s)₃, was unaffected by antagonists of Na⁺, Cat⁺, and Cl^- conductances, but was sensitive to changes in extracellular K⁺ concentration. The IP(s)₃-induced conductance was voltage-dependent, was activated in 10 ms with depolarization, and was blocked by extracellular Bat⁺ or intracellular Cat⁺ chelation. It was not suppressed by other K⁺ conductance antagonists. Thus, IP(s)₃, may activate a novel K⁺ conductance in CAI pyramidal cells. IP₃ itself did not elicit this conductance, suggesting it may be rapidly metabolized in these cells.