CHANGES IN MEMBRANE-POTENTIAL INDUCED BY LOCAL-ANESTHETIC BUPIVACAINEON MITOCHONDRIA WITHIN EHRLICH ASCITES TUMOR-CELLS

The effect of the local anesthetic bupivacaine on transmembrane potent ial of mitochondria within Ehrlich ascites tumor cells has been invest igated by the safranine method. The following summarizes the results. 1) When Ehrlich ascites tumor cells were added into a medium containin g safranine, a differential spectrum with a decrease at 520 nm appeare d. The addition of bupivacaine did not reverse the response but result ed in a spectrum similar to that observed with deenergized mitochondri a, with a maximum at 550 nm and a minimum at 495 nm. 2) The addition o f glucose to bupivacaine- or rotenone-treated cells also produced a sh ift in safranine spectrum similar to that observed upon energization o f mitochondrial membranes by ATP, thus suggesting that glycolytically generated ATP was responsible for this spectral change. 3) The ability of bupivacaine to decrease the membrane potential in mitochondria wit hin Ehrlich ascites tumor cells was due to two different effects: inhi bition of the energy-conserving site 1 of the respiratory chain and un coupling by a true protonophoretic mechanisma. Copyright (C) 1996 Else vier Science Inc.