Effects of the anaesthetic propofol on the calcium-induced permeability transition of rat heart mitochondria: direct pore inhibition and shift of the gating potential.

Mitochondrial calcium exchanges are involved in intracellular calcium homeostasis and in the contraction-relaxation process in myocytes. The calcium-induced permeability transition of the heart mitochondria inner membrane appears to be an important calcium efflux mechanism involved in some physiological and pathological situations. The negative inotropic effect of the anaesthetic propofol results in part from a decrease in intracellular calcium availability. Thus, this study evaluates the effects of propofol on calcium transport and permeability transition of heart mitochondria. The propofol-inhibition of the permeability transition of liver mitochondria was previously investigated [Eriksson, O. (1991) FEBS Lett. 279, 45-48] in such conditions that its uncoupling effect was not taken into account. We show here that propofol uncoupling results in a decrease in calcium uptake rate which could in part explain the decreased permeability transition rate. However, comparison of equipotent uncoupling concentrations of propofol and carbonylcyanide m-chlorophenylhydrazone reveals that beyond this uncoupling effect, propofol has a direct inhibitory action on the permeability transition pore, concomittant with a shift of its gating potential.