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PEDIATRIC ANESTHESIA

Ketamine Inhibits Inositol 1,4,5-Trisphosphate Production Depending on the Extracellular Ca²⁺ Concentration in Neonatal Rat Cardiomyocytes

Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Aomori, Japan

Address correspondence and reprint requests to Akira Kudoh, MD, Department of Anesthesiology, University of Hirosaki School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Aomori, Japan.

We investigated the effect of ketamine on inositol 1,4,5-trisphosphate (IP3) formation in rat cardiomyocytes. After the addition of 1 µmol/L ketamine, IP3 production in the presence of 0.5, 1, 5, 10, and 30 mmol/L Ca²⁺ significantly decreased from 537.1 ± 8.3, 590.7 ± 12.9, 690.6 ± 7.9, 754.8 ± 12.5, and 823.7 ± 15.2 pmol/mg protein to 467.0 ± 8.3, 483.8 ± 11.0, 512.6 ± 21.3, 612.1 ± 16.9, and 652.6 ± 17.3 pmol/mg protein, respectively. When exposed to TMB-8 (a intracellular calcium inhibitor), IP3 production decreased significantly from 347.2 ± 27.3 to 283.8 ± 20.4 pmol/mg protein in the presence of 1 µmol/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 Ca²⁺.