AJP - Renal Physiology, Vol 248, Issue 6 845-F850, Copyright © 1985 by American Physiological Society
In vitro versus in vivo mitochondrial calcium loading in ischemic acute renal failure
P. E. Arnold, D. Lumlertgul, T. J. Burke and R. W. Schrier
Progressive mitochondrial Ca2+ accumulation and respiratory dysfunction
have been observed during reperfusion after renal ischemia. The present
study demonstrated that normal mitochondria, isolated in the presence of
high Ca2+ concentrations, are capable of accumulating large amounts of Ca2+
in vitro and exhibit depressed respiratory rates. Since mitochondria
isolated from reperfused ischemic tissue may be exposed to high
concentrations of Ca2+ during the isolation procedure, the present study
examined the effect of in vitro versus in vivo mitochondrial Ca2+ loading
on mitochondrial function during ischemic acute renal failure (ARF) in
anesthetized rats. When ruthenium red was added during isolation to prevent
mitochondrial Ca2+ exchange with the medium, mitochondrial Ca2+ increased
from 10.8 +/- 0.3 to 65.6 +/- 11.6 nmol/mg (P less than 0.001) after 24 h
of postischemic reperfusion; this resulted in a 47% reduction in the
acceptor-control ratio (ACR) from 4.19 +/- 0.09 to 2.70 +/- 0.13 (P less
than 0.001). These data were compared with an increase in mitochondrial
Ca2+ from 52.5 +/- 2.9 to 167.6 +/- 25.4 nmol/mg (P less than 0.001) and a
95% fall in ACR (3.84 +/- 0.40 to 1.15 +/- 0.08, P less than 0.001) at 24 h
of reperfusion when no ruthenium red was added. However, at each time point
examined, in vivo mitochondrial Ca2+ accumulation was shown to account for
50% or more of the mitochondrial respiratory dysfunction observed during
ischemic ARF.
