Regulation of cardiac mitochondrial calcium by average extramitochondrial calcium

Autor: D. A. Scott, J. R. Leisey, Russell C. Scaduto, L. W. Grotyohann
Rok vydání: 1993
Předmět:
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 265:H1203-H1208
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.1993.265.4.h1203
Popis: A system to perifuse isolated rat heart mitochondria was designed to study the relationship between mitochondrial matrix free Ca2+ and extramitochondrial free Ca2+ under conditions in which the latter concentration could oscillate over a range typical of that expected in vivo. We tested the hypothesis that the level of intramitochondrial Ca2+ responds to the average extramitochondrial Ca2+ in the heart. Mitochondria were immobilized within an optical chamber for measurement of endogenous NAD(P)H and fura 2 fluorescence. NAD(P)H increased significantly on provision of substrates and decreased reversibly in the presence of ADP, indicating maintenance intact coupled respiration by this preparation. Matrix free Ca2+ was measured using fura 2-loaded mitochondria and, in parallel experiments, media free Ca2+ was measured with fura 2 in the absence of mitochondria. Oscillation of extramitochondrial Ca2+ from < 0.1 microM to approximately 2 microM at frequencies of 0.5, 1.0, and 1.25 cycles/s produced steady-state levels of matrix Ca2+ that were independent of frequency but proportional to the average media free Ca2+ concentration. Matrix Ca2+ increased to a steady state on an increase in the extramitochondrial average Ca2+ concentration with a half-time (t1/2) of approximately 2 min at 22 degrees C. Oscillation of mitochondrial Ca2+ was not observed under any conditions tested. The data are taken to indicate that in vivo, the concentration of mitochondrial matrix free Ca2+ is a steady state that is proportional to the average extramitochondrial Ca2+ concentration and that changes in the latter represent a mechanism of signal transduction from the cytosol to the mitochondrial matrix.
Databáze: OpenAIRE