From owner-metabolic-reg@net.bio.net Thu Oct 07 23:00:00 1993
Path: biosci!daresbury!doc.ic.ac.uk!uknet!pipex!uunet!mcsun!sun4nl!sara50!HASARA11.SARA.NL!V50ZBEEK
From: V50ZBEEK@HASARA11.SARA.NL (Hans van Beek (v50zbeek@vm1.sara.nl))
Newsgroups: bionet.metabolic-reg
Subject: control coefficients determined in intact heart
Keywords: cardiac oxygen consumption; contractility
Message-ID: <16C60DEFE.V50ZBEEK@HASARA11.SARA.NL>
Date: 8 Oct 93 08:08:43 GMT
Organization: S.A.R.A. Academic Computing Services Amsterdam
Lines: 31
Nntp-Posting-Host: vm1.sara.nl
X-Newsreader: NNR/VM S_1.3.2

Recently Jan Bart Hak and myself determined the flux control coefficient of
cardiac mitochondrial ATP synthesis over cardiac oxygen consumption in isolated
rabbit hearts.  We did this by partially blocking the ATP synthase by infusing
non-saturating amounts of oligomycin. We found a decline in oxygen consumption
after infusing oligomycin in the heart. Then we isolated the mitochondria at
the end of the perfusion experiment. Control experiments showed that the
inhibition by oligomycin was preserved during isolation of the mitochondria.
Then we determined the oxygen consumption in the isolated mitochondria during
stimulation with ADP and during uncoupling with FCCP, which essentially
bypasses the oligomycin inhibition. Thus we determined after the isolated
heart experiment to what extent the mitochondria had been inhibited with
oligomycin. The result was that the flux control coefficient was 0.26, i.e.,
cardiac oxygen consumption, and presumably ATP turnover decreases 2.6% for a
10% decrease in mitochondrial ATP synthetic capacity. The pressure developed
by the heart decreased 2.4% for the same 10% decrease in mitochondrial
capacity. Thus we found a functional control coefficient of 0.24 . It was
our impression that biochemists and cardiac physiologists generally believed
that cardiac ATP synthetic capacity is present in large excess and would
have very low flux control. We hope to put this in perspective by quantifying
the control strength. We don't know any examples where control coefficients
have been determined in intact organs. We would look forward to hear about
such examples.
If this abstract of our research turns out to be of interest we will inform
you on the control coefficients of transient times of oxygen consumption after
steps of cardiac workload which varied from -0.8 at low heart rates to 0 at
higher heart rates.
 
Hans van Beek  & Jan Bart Hak
Laboratory for Physiology
Free University
Amsterdam

.