INHIBITION AND ACTIVATION OF CALCIUM TRANSPORT IN MITOCHONDRIA . EFFECT OF LANTHANIDES AND LOCAL ANESTHETIC DRUGS

Using murexide to measure the Ca2+ accumulation rates and bromothymol blue to measure the rates of the intramitochondrial pH changes, and by measuring the oxidationreduction changes of the respiratory chain carriers during Ca2+ accumulation, it was found that lanthanides at a concentration of about 0.05-0.07 mμmole/mg of protein specifically inhibit the reactions of Ca2+ with the mitochondrial membranes and the accumulation of Ca2+ into the mitochondria. No other functions of the mitochondria were found to be inhibited. It was also found that local anesthetics like butacaine enhance the accumulation of Ca2+. Maximum activation was obtained at about 40 mμmoles/mg of protein. On the basis of these findings the nature of the mechanism of the mitochondrial divalent cation accumulation is discussed. It is suggested that in the mitochondria there exists a divalent cation carrier which can be identified and blocked by the lanthanides. This carrier is functionally specific and acts only as a divalent cation carrier. The functionally unspecific Ca2+ binding sites can be titrated with butacaine. By blocking the unspecific sites the Ca2+ accumulation can be enhanced. © 1969, American Chemical Society. All rights reserved.