Comparative kinetic analysis reveals that inducer-specific ion release precedes the mitochondrial permeability transition |
| |
Authors: | Boris F. Krasnikov Dmitry B. Zorov Andrey A. Zaspa Bruce S. Kristal Arthur J.L. Cooper Abraham M. Brown |
| |
Affiliation: | a Dementia Research Service, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA b A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia c Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA d Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA |
| |
Abstract: | Relationships among the multiple events that precede the mitochondrial membrane permeability transition (MPT) are not yet clearly understood. A combination of newly developed instrumental and computational approaches to this problem is described. The instrumental innovation is a high-resolution digital apparatus for the simultaneous, real-time measurement of four mitochondrial parameters as indicators of the respiration rate, membrane potential, calcium ion transport, and mitochondrial swelling. A computational approach is introduced that tracks the fraction of mitochondria that has undergone pore opening. This approach allows multiple comparisons on a single time scale. The validity of the computational approach for studying complex mitochondrial phenomena was evaluated with mitochondria undergoing an MPT induced by Ca2+, phenylarsine oxide or alamethicin. Selective ion leaks were observed that precede the permeability transition and that are inducer specific. These results illustrate the occurrence of inducer-specific sequential changes associated with the induction of the permeability transition. Analysis of the temporal relationship among the multiple mitochondrial parameters of isolated mitochondria should provide insights into the mechanisms underlying these responses. |
| |
Keywords: | MPT, membrane permeability transition ΔΨ, mitochondrial membrane potential PhAsO, phenylarsine oxide TPP+, tetraphenyl-phosphonium PC, personal computer LED, light-emitting diode PD, photodiode ADC, analog-digital converter DAC, digital-analog converter BSA, bovine serum albumin RLM, rat liver mitochondria RCR, respiratory control ratio CsA, cyclosporin A |
本文献已被 ScienceDirect 等数据库收录! |
|