N. Brustovetsky et M. Klingenberg, MITOCHONDRIAL ADP ATP CARRIER CAN BE REVERSIBLY CONVERTED INTO A LARGE CHANNEL BY CA2+/, Biochemistry, 35(26), 1996, pp. 8483-8488
Single-channel current measurements of excised patches with reconstitu
ted purified mitochondrial ADP/ATP carrier (AAC) indicates the presenc
e of a large low cation selective (P-K+/P-Cl- = 4.3 +/- 0.6) channel.
The channel conductance has multiple sublevels and varies from 300 to
600 pS. It has low probability of current fluctuations at V-hold up to
80-100 mV of both signs and is reversibly gated at V-hold > 150 mV. T
he opening of the channel is Ca2+-dependent (1 mM Ca2+) and can be rev
ersibly closed on removal of Ca2+. It is strongly pH dependent and clo
ses completely at pH(ex) 5.2. The AAC-specific inhibitor bongkrekate i
nhibits the channel partially and completely in combination with ADP,
whereas carboxyatractylate did not affect the conductance. The effects
of these AAC-specific ligands prove that the channel activity belongs
to AAC. The AAC-linked conductance can clearly be differentiated from
the porin channel, rarely detected in our preparations. The propertie
s of the AAC-linked channel coincide with the mitochondrial permeabili
ty transition pore (MTP), which is also affected by the AAC ligands [H
unter, D. R., & Haworth, R. A. (1979) Arch. Biochem. Biophys. 195, 453
-459] and resembles the mitochondrial ''multiconductance channel'' [Ki
nnally, K. W., Campo, M. L., & Tedeschi, H. T. (1989) J. Bioenerg. Bio
membr. 21, 497-506] or ''megachannel'' [Petronilli, V., Szabo, I., & Z
oratti, M. (1989) FEES Lett. 259, 137-143]. Therefore we conclude that
the AAC, when converted into a large unselective channel, is a key co
mponent in the MTP and thus is involved in the ischemia-reperfusion da
mage and cytosolic Ca2+ oscillations. The channel opening in AAC is pr
oposed to be caused by binding of Ca2+ to the cardiolipin, tightly bou
nd to AAC, thus releasing positive charges within the AAC which open t
he gate.