(Circulation. 2001;103:1303.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
- and ß-Subunits in Rat and Mouse Cardiac Myocytes
From the Departments of Pharmacology (J.D.M., C.C., L.N.M., L.L.I.) and Internal Medicine (R.M., F.C.B.), University of Michigan, Ann Arbor, and Department of Pharmacology (I.R., H.A., R.S.K.), Columbia University, College of Physicians and Surgeons, New York, NY.
Correspondence to Lori L. Isom, PhD, Department of Pharmacology, The University of Michigan, 1301 MSRB III, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0632. E-mail lisom{at}umich.edu
BackgroundSodium
channels isolated from mammalian brain are composed of
-,
ß1-, and ß2-subunits.
The composition of sodium channels in cardiac muscle, however, has not
been defined, and disagreement exists over which ß-subunits are
expressed in the myocytes. Some investigators have demonstrated
ß1 expression in heart. Others have not
detected any auxiliary subunits. On the basis of Northern blot analysis
of total RNA, ß2 expression has been thought
to be exclusive to neurons and absent from cardiac
muscle.
Methods and ResultsThe
goal of this study was to define the subunit composition of cardiac
sodium channels in myocytes. We show that cardiac sodium channels are
composed of
-, ß1-, and
ß2-subunits. Nav1.5 and Nav1.1 are expressed
in myocytes and are associated with ß1- and
ß2-subunits. Immunocytochemical localization
of Nav1.1, ß1, and ß2
in adult heart sections showed that these subunits are expressed at the
Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with
ß2 in transfected cells resulted in no
detectable changes in sodium current.
ConclusionsCardiac
sodium channels are composed of
- (Nav1.1 or Nav1.5),
ß1-, and ß2-subunits.
Although ß1-subunits modulate cardiac sodium
channel current, ß2-subunit function in heart
may be limited to cell
adhesion.
Key Words: cells signal transduction genes ion channels
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