Effects of inositol, 1,4,5-trisphosphate injections into cat spinal motoneurons.

Inositol 1,4,5-trisphosphate (IP3) was injected iontophoretically into cat spinal motoneurons in pentobarbital-anaesthetized cats and nonanaesthetized, decerebrate cats. Injections of IP3 induced a long-lasting, reproducible hyperpolarization without consistent change in input resistance. The peak amplitude of post-spike afterhyperpolarization (AHP) was significantly increased by IP3 when the membrane potential was adjusted to the control level. Intracellular injections of Ca2+ chelators, which depressed the Ca2(+)-activated AHP, prevented the IP3-induced long-lasting hyperpolarization, suggesting that IP3 acts by a Ca2(+)-dependent mechanism. Intracellular injections of myo-inositol did not consistently induce hyperpolarizations. Also intracellular injections of Li+, which blocks IP3 catabolism, did not prevent the IP3-evoked hyperpolarization. These data suggest that IP3 itself, rather than its breakdown product myo-inositol, is mainly responsible for the hyperpolarizing effect. Possible mechanisms for the IP3-induced hyperpolarization are discussed.