Inositol 1,4,5-trisphosphate (1,4,5-InsP 3 ) was perfused into rat dorsal root ganglion (DRG) neurons by whole-cell patch-clamp electrodes, while measuring the membrane potential. This operation evoked a transient (2-3 min) membrane hyperpolarization of about -15 mV (from -42 mV) followed by a depolarization. The membrane hyperpolarization was abolished when 30 mM EGTA was perfused together with 1,4,5-InsP 3 or when 0.2 mM quinine was added to the bath solution. The hyperpolarizing response was enhanced when a low-Ca 2 + EGTA-free intracellular solution was used. Two InsP 2 isomers induced a different response. Our results suggest that the hyperpolarization is due to 1,4,5-InsP 3 - induced Ca 2 + release which may trigger Ca-sensitive K + channels to open. Present results show that cultured DRG neurons are able to respond to 1,4,5-InsP 3 perfusion in the whole-cell configuration.