Chronic renal failure increases cytosolic calcium of
hepatocytes
Klin, Mariusz, Miroslaw Smogorzewski, Shaul G. Massry.
Division of Nephrology and the Department of Medicine, University
of Southern California School of Medicine, Los Angeles, CA 90033.
APStracts 2:0047G, 1995.
CRF is associated with increased calcium content of liver and reduced
hepatic lipase activity. This has been attributed to a rise in
cytosolic calcium ([Ca2+]) of the hepatocytes, but data on this issue
are lacking. We examined the [Ca2+]i and ATP content of hepatocytes
as well as the activity of Na+-K+ ATPase, Ca2+ ATPase and Na+-Ca2+
exchanger of hepatic membranes vesicles from normal rats, animals
with 6 weeks of CRF, CRF normocalcemic parathyroidectomized (CRF-PTX)
rats and CRF and normal animals treated with verapamil (CRF-V,
normal-V). [Ca2+]i in hepatocytes of CRF rats was higher (281+7.4 nM)
and ATP lower (6.4+1.8 nmoles/mg protein) than in normal (209+5.3 nM;
12.5+0.89 nmoles/mg protein), CRF-PTX (212+1.0 nM; 13.7+0.79
nmoles/mg protein), normal-V (215+2.3 nM; 14.2+0.77
nmoles/mg/protein), CRF-V (209+7.4 nM; 14.8+0.72 nmoles/106 cells).
The Na+-K+ ATPase, the Vmax of Ca2+ ATPase and the activity of Na+
-Ca2+ exchanger were reduced while the Km of Ca2+ ATPase was increased
in CRF rats as compared to the 4 groups of rats. The values in the
latter group were not different. These results indicate that 1) in
CRF, the hepatocytes are overloaded with calcium, 2) this is due to
excess PTH of CRF since PTX-CRF rats had normal levels of [Ca2+]i, 3)
the increase in [Ca2+]i is due to two processes a) PTH-induced
increased entry into hepatocytes since treatment of CRF ras with
verapamil which blocks the action of PTH prevented the rise in
[Ca2+]i, and b) decreased calcium extrusion out of these cells due to
impaired activities of Ca2+ ATPase, Na+-K+ ATPase, and Na+-Ca2+
exchanger.
Received 6 September 1994; accepted in final form 21 February
1995.
APS Manuscript Number G336-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 March 1995.