© 1996 American Heart Association, Inc.
Articles |
The 
3 Isoform Protein of the Na+,K+-ATPase Is Associated With the Sites of Cardiac and Neuromuscular Impulse Transmission
From the Departments of Internal Medicine, Physiology, Neurology, and Pathology, Yale University School of Medicine, New Haven, Conn.
Correspondence to Raphael Zahler, MD, PhD, Section of Cardiology, Fitkin 3, Yale University School of Medicine, 333 Cedar St, New Haven CT 06510.
Abstract The 
(catalytic) subunit of the Na+
pump (Na+,K+-ATPase) has three isoforms:
1 is ubiquitous, skeletal muscle expresses predominantly 2, and
3 has been localized to specific types of neurons and, possibly, to
axonal processes. The 3 isoform mRNA is also expressed in the rat
cardiac conduction system. Thus, we studied rat heart and quadriceps
muscles by immunohistochemistry using isoform-specific antibodies
to the Na+ pump subunit and labeled
-bungarotoxin as a probe for the neuromuscular junction (NMJ).
We found that 3 pump protein is localized to three sites important
for impulse transmission: the junctional complex between cardiac
myocytes, the heart conduction system, and the NMJ. Specifically, all
levels of the conduction system expressed 3 immunoreactive protein,
as assessed by two isoform-specific antibodies and
histological conduction system markers. Specific
expression at the junctional complex was confirmed by immuno-EM.
Double-labeling and denervation analysis indicated that
3-positive areas in skeletal muscle were presynaptic and adjacent to
postsynaptic bungarotoxin-positive regions, which had the classic
morphology of NMJs. Thus, specific
Na+,K+-ATPase pump isoforms may be
adapted to maintenance of membrane potential and/or
intracellular ion concentrations required for impulse transmission in
both heart and presynaptic motor terminals contacting skeletal muscle.
Key Words: Na+,K+-ATPase isoform • neuromuscular junction • cardiac conduction system
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