Ketamine Inhibits Inositol 1,4,5-Trisphosphate Production Depending on the Extracellular Ca Concentration in Neonatal Rat Cardiomyocytes

We investigated the effect of ketamine on inositol 1,4,5trisphosphate (IP3) formation in rat cardiomyocytes. After the addition of 1 mmol/L ketamine, IP3 production in the presence of 0.5, 1, 5, 10, and 30 mmol/L Ca significantly decreased from 537.1 6 8.3, 590.7 6 12.9, 690.6 6 7.9, 754.8 6 12.5, and 823.7 6 15.2 pmol/mg protein to 467.0 6 8.3, 483.8 6 11.0, 512.6 6 21.3, 612.1 6 16.9, and 652.6 6 17.3 pmol/mg protein, respectively. When exposed to TMB-8 (a intracellular calcium inhibitor), IP3 production decreased significantly from 347.2 6 27.3 to 283.8 6 20.4 pmol/mg protein in the presence of 1 mmol/L ketamine, but A23187, which increases intracellular calcium, did not affect the inhibition of IP3 production by ketamine. These results demonstrate that ketamine decreases IP3 formation through inhibition of the calcium ion-sensing receptor and that IP3 formation reduced by ketamine is not affected by the alteration of intracellular calcium. Implications: Ketamine has a negative inotropic effect in isolated cardiomyocytes. The negative inotropic effect was associated with a decrease in inositol 1,4,5-trisphosphate production, and the inhibitory action was enhanced depending on the concentration of extracellular Ca. (Anesth Analg 1999;89:1417–22)