Bs. Wong et Cd. Martin, KETAMINE INHIBITION OF CYTOPLASMIC CALCIUM SIGNALING IN RAT PHEOCHROMOCYTOMA (PC-12) CELLS, Life sciences, 53(22), 1993, pp. 359-364
This study examines the mechanism of action of ketamine, a dissociativ
e anesthetic, with a specific focus on its ability to inhibit changes
in the concentration of intracellular free calcium, [Ca2+]i, in PC-12
cells. The resting [Ca2+]i as measured with the fluorescent probe Fura
-2 AM in control cells is 184.8 +/- 8.6 nM (mean +/- SEM, n = 15). Cha
nges in [Ca2+]i via influx through voltage-gated calcium channels afte
r membrane depolarization with potassium chloride were monitored in th
e absence and presence of various concentrations of ketamine. Potassiu
m-depolarization caused a dose-dependent rapid increase in [Ca2+]i, av
eraging 62 +/- 5%, 33 +/- 2% and 18 +/- 3% (n = 10 each) above control
levels for 70 mM, 50 mM and 35 mM KCl, respectively. Ketamine, in the
dosage range studied (5 - 500 muM), inhibited the increase in [Ca2+]i
stimulated by potassium-depolarization in a dose-dependent manner. Th
e computer-fitted dose-response curve of the pooled data yielded a hal
f maximal suppression concentration, ED50, of 33 muM. In conclusion, t
his study demonstrates that ketamine inhibits Ca2+ influx through volt
age-gated Ca2+ channels in PC-12 cells at clinically relevant doses, a
nd may play a role in ketamine's action as a general anesthetic agent.