Published Online
on March 8, 2004

A more recent version of this article appeared on March 23, 2004

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Submitted on November 21, 2002
Revised on December 5, 2003
Accepted on December 9, 2003

Distinct Subcellular Localization of Different Sodium Channel and Subunits in Single Ventricular Myocytes From Mouse Heart

Sebastian K.G. Maier MD, Ruth E. Westenbroek PhD, Kimberly A. McCormick PhD, Rory Curtis PhD, Todd Scheuer PhD, and William A. Catterall PhD^*

From the Department of Pharmacology, University of Washington, Seattle (S.K.G.M. R.E.W., K.A.M., T.S., W.A.C.); Medizinische Universitätsklinik Würzburg, Würzburg, Germany (S.K.G.M.); and Elixir Pharmaceuticals, Cambridge, Mass (R.C.).

^* To whom correspondence should be addressed. E-mail: wcatt{at}u.washington.edu.

Background--Voltage-gated sodium channels composed of pore-forming and auxiliary subunits are responsible for the rising phase of the action potential in cardiac muscle, but their localizations have not yet been clearly defined.

Methods and Results--Immunocytochemical studies show that the principal cardiac subunit isoform Na_v1.5 and the 2 subunit are preferentially localized in intercalated disks, identified by immunostaining of connexin 43, the major protein of cardiac gap junctions. The brain subunit isoforms Na_v1.1, Na_v1.3, and Na_v1.6 are preferentially localized with 1 and 3 subunits in the transverse tubules, identified by immunostaining of -actinin, a cardiac z-line protein. The 1 subunit is also present in a small fraction of intercalated disks. The recently cloned 4 subunit, which closely resembles 2 in amino acid sequence, is also expressed in ventricular myocytes and is localized in intercalated disks as are 2 and Na_v1.5.

Conclusions--Our results suggest that the primary sodium channels present in ventricular myocytes are composed of Na_v1.5 plus 2 and/or 4 subunits in intercalated disks and Na_v1.1, Na_v1.3, and Na_v1.6 plus 1 and/or 3 subunits in the transverse tubules.

Key words: ion channels • sodium • myocytes • ventricles • immunohistochemistry

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