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

Abstract

Background— Voltage-gated sodium channels composed of pore-forming α and auxiliary β 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 α subunit isoform Na v 1.5 and the β2 subunit are preferentially localized in intercalated disks, identified by immunostaining of connexin 43, the major protein of cardiac gap junctions. The brain α subunit isoforms Na v 1.1, Na v 1.3, and Na v 1.6 are preferentially localized with β1 and β3 subunits in the transverse tubules, identified by immunostaining of α-actinin, a cardiac z-line protein. The β1 subunit is also present in a small fraction of intercalated disks. The recently cloned β4 subunit, which closely resembles β2 in amino acid sequence, is also expressed in ventricular myocytes and is localized in intercalated disks as are β2 and Na v 1.5. Conclusions— Our results suggest that the primary sodium channels present in ventricular myocytes are composed of Na v 1.5 plus β2 and/or β4 subunits in intercalated disks and Na v 1.1, Na v 1.3, and Na v 1.6 plus β1 and/or β3 subunits in the transverse tubules.