The effects of ketamine on Ca2+ movements in A7r5 vascular smooth muscle cells.

Abstract

To investigate the effects of ketamine on Ca2+ movement to and from intracellular Ca2+ stores and across plasma membranes, 45Ca2+ fluxes were studied in permeabilized and intact A7r5 smooth muscle cells, an established cell line derived from embryonic rat aorta. Monolayers of A7r5 cells were loaded with 45Ca2+, and the radioactivity in the collected medium and the residual activity were measured by liquid scintillation counting. Ketamine had no effect on 45Ca2+ uptake and passive leak of the nonmitochondrial Ca2+ pool in permeabilized A7r5 cells. Ketamine 1 mM had no inhibitory effect on the inositol 1,4,5-trisphosphate (InsP3, 1 microM)-induced Ca2+ release from the intracellular stores. In intact A7r5 cells, ketamine did not alter the Ca2+ extrusion from these cells under resting conditions. Addition of 10 nM vasopressin resulted in a transient Ca2+ release from the intracellular stores. Ketamine inhibited this vasopressin-induced Ca2+ release, but did not enhance Ca2+ extrusion through the plasma membrane in the period after the vasopressin effect. These results indicate that ketamine inhibits agonist-induced Ca2+ release from intracellular stores, but has no effect on Ca(2+)-uptake into intracellular stores or on Ca2+ extrusion through the plasma membrane in A7r5 smooth muscle cells.