Reciprocal regulation of cardiac na,k-atpase and na-ca exchanger
abundance: hypertension, thyroid hormone and amiodarone.
Magyar, Clara E., Jiangnan Wang, Kay K. Azuma, and Alicia A.
McDonough.
Department of Physiology and Biophysics, University of Southern
California School of Medicine
APStracts 2:0149C, 1995.
Inhibiting cardiac sodium pump activity decreases the driving force
for Na+-Ca++ exchanger transport which increases cellular Ca++ stores
and contractility. Decreased abundance of sodium pumps would be
expected to have the same effect as decreased activity unless there
was reciprocal regulation of Na+-Ca++ exchanger expression to oppose
the effects of depressed sodium pump activity on intracellular Ca++
stores. The aim of this study was to test the hypothesis that cardiac
Na+-Ca++ exchanger abundance is regulated in a reciprocal fashion to
Na,K-ATPase abundance in a number of models known to have altered
Na,K-ATPase abundance. In renovascular hypertension, cardiac
ventricle Na,K-ATPase 1 levels are unaltered, 2 isoform subunit mRNA
and protein levels decrease to 0.76 0.06 and 0.56 0.07 of control,
respectively, and Na+-Ca++ exchanger protein (not mRNA) increased
1.35 0.11 fold. In the transition from hypothyroid to hyperthyroid,
cardiac 1doubles, 2 protein increases 8.83 1.06 fold and Na+-Ca++
exchanger protein decreases to 0.64 0.11. A similar pattern was seen
during cardiac development in the pre-weaning rat heart. Treatment
with the antiarrhythymic amiodarone has no effect on 1, decreases 2
protein expression to 0.51 0.08 of control and increases exchanger
expression 1.42 0.16 fold. In conclusion, the reciprocal regulation
of Na+-Ca++ exchanger and Na,K-ATPase 2 expression provides evidence
for a homeostatic mechanism which would oppose the changes in
cellular Ca++ stores driven by the changes in Na,K-ATPase activity.
Received 15 August 1994; accepted in final form 13 March 1995.
APS Manuscript Number C487-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 March 1995.