Na,k-atpase [alpha] isoform protein expression in heart and
vascular endothelium: cellular and developmental regulation.
Zahler, Raphael, Wei Sun, Thomas Ardito, and Michael Kashgarian.
DEPARTMENTS OF INTERNAL MEDICINE AND PATHOLOGY, YALE UNIVERSITY
SCHOOL OF MEDICINE, NEW HAVEN CT 06510
APStracts 2:0343C, 1995.
The sodium pump (Na,K-ATPase) is important for regulation of membrane
potential and transport in smooth muscle and heart. The a (catalytic)
subunit of this pump has three isoforms: [alpha]1 is ubiquitous, but
[alpha]2 and [alpha]3 are mainly localized to excitable tissue.
Physiologic differences between isoforms are not completely
understood, but [alpha]3 pumps appear to have a lower affinity for
intracellular sodium and a higher ouabain affinity than [alpha]1
pumps. The [alpha]2 and [alpha]3 isoform mRNA's are expressed at high
levels in normal adult rat cardiac conduction system. While [alpha]1
and [alpha]3 are both globally expressed in neonatal rat myocardium,
there is a switch in the myocardial isoform pattern from [alpha]3 to
[alpha]2 after birth. There are also important species differences in
cardiac isoform patterns. Furthermore, changes in Na,K-ATPase
isoforms in heart and vascular tissue have been reported in
association with hypertension, but little is known about isoform
expression in normal endothelium. We therefore studied the cellular
distribution of sodium pump protein isoforms in neonatal and adult
myocardium and endothelium. Results: Immunohistochemical analysis of
rat tissues showed that the [alpha]1 isoform was expressed throughout
atrial and ventricular myocardium, with [alpha]1 the only isoform
detectable in the adult t-tubule system. While [alpha]2 was also
present in ventricular myocytes, signal was markedly stronger in
conduction tissue and papillary muscle. In hearts from neonatal rats,
the [alpha]3 isoform predominated in the cardiac conduction system,
while [alpha]2 was not detectable in any structure except vascular
endothelium. In tissues and in cell lines representing a variety of
species and vessel sizes, endothelium of large vessels expressed
primarily [alpha]1, while [alpha]2 could be detected in endothelium
of small vessels in rat heart. No evidence of [alpha]3 expression in
endothelium was found. Thus, the complex spatial and developmental
regulation of sodium pump isoform expression in cardiovascular
tissues may provide additional correlates to distinct physiologic
roles of these transporters.
Received 17 January 1995; accepted in final form 25 July 1995.
APS Manuscript Number C33-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95